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Ephedrine
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<h2 id="medical-uses">Medical uses</h2> <p>Ephedrine is a non-<a href="/facts/Catecholamine/hHFrCMgM">catecholamine</a> <a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a> with cardiovascular effects similar to those of <a href="/facts/Adrenaline/k7vvMI7E">adrenaline</a> (epinephrine): increased blood pressure, heart rate, and contractility. Like <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>, it is a <a href="/facts/Bronchodilator/IQMu7bra">bronchodilator</a>, with pseudoephedrine having considerably less effect.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> </p><p>Ephedrine may decrease <a href="/facts/Motion_sickness/kBs72ygo">motion sickness</a>, but it has mainly been used to decrease the sedating effects of other medications used for motion sickness.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p><p>Ephedrine is also found to have quick and long-lasting responsiveness in <a href="/facts/Congenital_myasthenic_syndrome/GgPavkIT">congenital myasthenic syndrome</a> in early childhood and also even in adults with a novel <a href="/facts/COLQ/zVRBFgjP">COLQ</a> mutation.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p><p>Ephedrine is administered by intravenous boluses. Redosing usually requires increased doses to offset the development of <a href="/facts/Tachyphylaxis/V7VbY2Bo">tachyphylaxis</a>, which is attributed to the depletion of catecholamine stores.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p> <h3>Weight loss</h3> <p>Ephedrine promotes modest short-term <a href="/facts/Weight_loss/DQE4cXw0">weight loss</a>,<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> specifically fat loss, but its long-term effects are unknown.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> In mice, ephedrine is known to stimulate <a href="/facts/Thermogenesis/aA6HD0At">thermogenesis</a> in the <a href="/facts/Brown_adipose_tissue/ut8P9TLS">brown adipose tissue</a>, but because adult humans have only small amounts of brown fat, thermogenesis is assumed to take place mostly in the <a href="/facts/Skeletal_muscle/en1tVYFN">skeletal muscle</a>. Ephedrine also decreases <a href="/facts/Gastric_emptying/Q4PPDGT6">gastric emptying</a>. <a href="/facts/Methylxanthine/3ARA2QCg">Methylxanthines</a> such as <a href="/facts/Caffeine/Hx6E2QC5">caffeine</a> and <a href="/facts/Theophylline/qJzjQVB2">theophylline</a> have a synergistic effect with ephedrine for weight loss. This led to the creation and marketing of compound products.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> One of them, known as the <a href="/facts/ECA_stack/lo882kg5">ECA stack</a>, contains ephedrine with caffeine and aspirin. It is a popular supplement taken by <a href="/facts/Bodybuilding/Ggt22bNA">bodybuilders</a> seeking to cut body fat before a competition.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> A 2021 systematic review found that ephedrine led to a 2 kilograms (4.4 lb) weight loss greater than placebo, raised <a href="/facts/Heart_rate/YngB0bzg">heart rate</a>, and reduced <a href="/facts/LDL/R5VLPxAg">LDL</a> and raised <a href="/facts/High-density_lipoprotein/x7cs1ys9">HDL</a>, with no statistically significant difference in <a href="/facts/Blood_pressure/VtqqSM2J">blood pressure</a>.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> </p> <h3>Available forms</h3> <p class="note">See also: <a href="/facts/Theophylline/ephedrine/vdW17Hho">Theophylline/ephedrine</a></p> <p>Ephedrine is available as a <a href="/facts/Prescription_drug/a2zNYPMq">prescription-only</a> <a href="/facts/Pharmaceutical_drug/h9mhwWP2">pharmaceutical drug</a> in the form of an <a href="/facts/Intravenous/AwwuD3Nu">intravenous</a> <a href="/facts/Solution_(chemistry)/MGchhMQV">solution</a>, under brand names including Akovaz, Corphedra, Emerphed, and Rezipres as well as in <a href="/facts/Generic_drug/IF6AXDVX">generic forms</a>, in the United States.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> It is also available <a href="/facts/Over-the-counter_drug/QI3FcgRf">over-the-counter</a> in the form of 12.5 and 25 mg <a href="/facts/Oral_administration/vNQcvLVx">oral</a> <a href="/facts/Tablet_(pharmacy)/PcYmnjd0">tablets</a> for use as a <a href="/facts/Bronchodilator/IQMu7bra">bronchodilator</a> and as a 0.5% concentration <a href="/facts/Nasal_spray/zLm4BmWx">nasal spray</a> for use as a <a href="/facts/Decongestant/Vthbc5a0">decongestant</a>.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> The drug is additionally available in <a href="/facts/Combination_drug/pVS5UD72">combination</a> with <a href="/facts/Guaifenesin/6M5ShWzC">guaifenesin</a> in the form of oral tablets and liquids.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> Ephedrine is provided as the <a href="/facts/Hydrochloride/7Sdqua4a">hydrochloride</a> or <a href="/facts/Sulfate/yuWVxsUf">sulfate</a> <a href="/facts/Salt_(chemistry)/lsSKwGpn">salt</a> in pharmaceutical formulations.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a><a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h2 id="contraindications">Contraindications</h2> <p>Ephedrine should not be used in conjunction with certain <a href="/facts/Antidepressant/N62ND3Fa">antidepressants</a>, namely <a href="/facts/Norepinephrine%E2%80%93dopamine_reuptake_inhibitor/Y4Bg2Bkd">norepinephrine–dopamine reuptake inhibitors</a> (NDRIs), as this increases the risk of symptoms due to excessive serum levels of norepinephrine. </p><p><a href="/facts/Bupropion/wjWDPxmr">Bupropion</a> is an example of an antidepressant with an amphetamine-like structure similar to ephedrine, and it is an NDRI. Its action bears more resemblance to amphetamine than to <a href="/facts/Fluoxetine/U28lM3Pm">fluoxetine</a> in that its primary mode of therapeutic action involves norepinephrine and to a lesser degree dopamine, but it also releases some <a href="/facts/Serotonin/EzY58q4a">serotonin</a> from presynaptic clefts. It should not be used with ephedrine, as it may increase the likelihood of side effects. </p><p>Ephedrine should be used with caution in patients with inadequate fluid replacement, impaired adrenal function, <a href="/facts/Hypoxia_(medical)/JWV04G89">hypoxia</a>, <a href="/facts/Hypercapnia/wBArR1mW">hypercapnia</a>, <a href="/facts/Acidosis/hmfAo1uR">acidosis</a>, <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>, <a href="/facts/Hyperthyroidism/H9Eqmbgk">hyperthyroidism</a>, <a href="/facts/Prostatic_hypertrophy/ocGSCVK9">prostatic hypertrophy</a>, <a href="/facts/Diabetes_mellitus/2xeHXbsI">diabetes mellitus</a>, <a href="/facts/Cardiovascular/WXwudzzc">cardiovascular</a> disease, during delivery if maternal blood pressure is >130/80 mmHg, and during lactation.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> </p><p><a href="/facts/Contraindications/HawhU8x9">Contraindications</a> for the use of ephedrine include: <a href="/facts/Glaucoma/MWqWVNz3">closed-angle glaucoma</a>, <a href="/facts/Phaeochromocytoma/83IHw9gQ">phaeochromocytoma</a>, <a href="/facts/Hypertrophic_cardiomyopathy/NmPkh1rh">asymmetric septal hypertrophy</a> (idiopathic hypertrophic subaortic stenosis), concomitant or recent (previous 14 days) <a href="/facts/Monoamine_oxidase_inhibitor/obewT56a">monoamine oxidase inhibitor</a> (MAOI) therapy, general <a href="/facts/Anesthesia/b3MKVn8E">anesthesia</a> with halogenated hydrocarbons (particularly <a href="/facts/Halothane/PQ58E6ah">halothane</a>), tachyarrhythmias or ventricular fibrillation, or hypersensitivity to ephedrine or other stimulants. </p><p>Ephedrine should not be used at any time during pregnancy unless specifically indicated by a qualified physician and only when other options are unavailable.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> </p> <h2 id="side-effects">Side effects</h2> <p>Ephedrine is a potentially dangerous natural compound; as of 2004<a href="https://en.wikipedia.org/w/index.php?title=Ephedrine&action=edit">[update]</a> the US <a href="/facts/Food_and_Drug_Administration/rCEnh9WB">Food and Drug Administration</a> (FDA) had received over 18,000 reports of adverse effects in people using it.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> </p><p><a href="/facts/Adverse_drug_reaction/Ea0ktF6J">Adverse drug reactions</a> (ADRs) are more common with systemic administration (e.g. injection or oral administration) compared to topical administration (e.g. nasal instillations). ADRs associated with ephedrine therapy include <a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> </p> <ul><li>Cardiovascular: <a href="/facts/Tachycardia/ycmyzP7q">tachycardia</a>, cardiac <a href="/facts/Heart_arrhythmia/ooEpr46Q">arrhythmias</a>, <a href="/facts/Angina_pectoris/rT1brdwS">angina pectoris</a>, <a href="/facts/Vasoconstriction/9hdY0aR2">vasoconstriction</a> with <a href="/facts/Hypertension/wlAvBfcf">hypertension</a></li> <li><a href="/facts/Dermatology/YfvJ8uXn">Dermatological</a>: flushing, sweating, <a href="/facts/Acne_vulgaris/TKJxhHSd">acne vulgaris</a></li> <li><a href="/facts/Gastrointestinal_tract/nK2zwqBS">Gastrointestinal</a>: nausea</li> <li><a href="/facts/Genitourinary_system/u262MFXg">Genitourinary</a>: decreased urination due to vasoconstriction of renal arteries, difficulty urinating is not uncommon, as alpha-agonists such as ephedrine constrict the internal urethral sphincter, mimicking the effects of sympathetic nervous system stimulation</li> <li><a href="/facts/Nervous_system/CDxRKU2U">Nervous system</a>: restlessness, <a href="/facts/Confusion/Pcvw6deb">confusion</a>, <a href="/facts/Insomnia/C1TnQTb2">insomnia</a>, mild euphoria, <a href="/facts/Mania/qYV8BBbt">mania</a>/<a href="/facts/Hallucinations/5eUvLcnp">hallucinations</a> (rare except in previously existing psychiatric conditions), <a href="/facts/Delusions/cNsg7R41">delusions</a>, <a href="/facts/Formication/jBbenwvE">formication</a> (may be possible, but lacks documented evidence) <a href="/facts/Paranoia/Vytxdqa8">paranoia</a>, <a href="/facts/Hostility/jDsodz8R">hostility</a>, <a href="/facts/Panic/WGBRaa5o">panic</a>, <a href="/facts/Psychomotor_agitation/n1vWk6RD">agitation</a></li> <li><a href="/facts/Respiratory_system/IG8v5JEr">Respiratory</a>: <a href="/facts/Dyspnea/1jBfFzxU">dyspnea</a>, pulmonary edema</li> <li>Miscellaneous: dizziness, headache, tremor, <a href="/facts/Hyperglycemia/HM8eNqfX">hyperglycemic</a> reactions, dry mouth</li></ul> <h2 id="overdose">Overdose</h2> <p><a href="/facts/Overdose/Jlo2AX3Y">Overdose</a> of ephedrine may result in <a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a> <a href="/facts/Symptom/BzP6MrTN">symptoms</a> like <a href="/facts/Tachycardia/ycmyzP7q">tachycardia</a> and <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>. </p> <h2 id="interactions">Interactions</h2> <p>Ephedrine with <a href="/facts/Monoamine_oxidase_inhibitor/obewT56a">monoamine oxidase inhibitors</a> (MAOIs) like <a href="/facts/Phenelzine/lwCH0IDJ">phenelzine</a> and <a href="/facts/Tranylcypromine/YVIArwgA">tranylcypromine</a> can result in <a href="/facts/Hypertensive_crisis/dDPo1RB3">hypertensive crisis</a>. </p> <h2 id="pharmacology">Pharmacology</h2> <h3>Pharmacodynamics</h3> Monoamine release by ephedrine and related agents (<a href="/facts/Half_maximal_effective_concentration/x7oD7ITx">EC50</a>Tooltip half maximal effective concentration, nM)<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a><a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a><table><tbody><tr><th>Compound</th><th><a href="/facts/Norepinephrine/AjTIC9ox">NE</a>Tooltip Norepinephrine</th><th><a href="/facts/Dopamine/5gNy8Xkd">DA</a>Tooltip Dopamine</th><th><a href="/facts/Serotonin/EzY58q4a">5-HT</a>Tooltip Serotonin</th><th>Ref</th></tr><tr><td><a href="/facts/Dextroamphetamine/SoVP3mKN">Dextroamphetamine</a> (<i>S</i>(+)-amphetamine)</td><td>6.6–7.2</td><td>5.8–24.8</td><td>698–1765</td><td><a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a><a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a></td></tr><tr><td><a href="/facts/Cathinone/wDASEcYS"><i>S</i>(–)-Cathinone</a></td><td>12.4</td><td>18.5</td><td>2366</td><td><a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a></td></tr><tr><td>Ephedrine ((–)-ephedrine)</td><td>43.1–72.4</td><td>236–1350</td><td>>10000</td><td><a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a></td></tr><tr><td>(+)-Ephedrine</td><td>218</td><td>2104</td><td>>10000</td><td><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a><a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a></td></tr><tr><td><a href="/facts/Dextromethamphetamine/vS1jloMe">Dextromethamphetamine</a> (<i>S</i>(+)-methamphetamine)</td><td>12.3–13.8</td><td>8.5–24.5</td><td>736–1291.7</td><td><a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a><a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a></td></tr><tr><td><a href="/facts/Levomethamphetamine/cCyAAb1Q">Levomethamphetamine</a> (<i>R</i>(–)-methamphetamine)</td><td>28.5</td><td>416</td><td>4640</td><td><a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a></td></tr><tr><td><a href="/facts/Phenylpropanolamine/Bp2fDnBs">(+)-Phenylpropanolamine</a> ((+)-norephedrine)</td><td>42.1</td><td>302</td><td>>10000</td><td><a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a></td></tr><tr><td><a href="/facts/Phenylpropanolamine/Bp2fDnBs">(–)-Phenylpropanolamine</a> ((–)-norephedrine)</td><td>137</td><td>1371</td><td>>10000</td><td><a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a></td></tr><tr><td><a href="/facts/Cathine/ao34ryP7">Cathine</a> ((+)-norpseudoephedrine)</td><td>15.0</td><td>68.3</td><td>>10000</td><td><a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a></td></tr><tr><td><a href="/facts/L-Norpseudoephedrine/XQn6K9es">(–)-Norpseudoephedrine</a></td><td>30.1</td><td>294</td><td>>10000</td><td><a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a></td></tr><tr><td>(–)-Pseudoephedrine</td><td>4092</td><td>9125</td><td>>10000</td><td><a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a></td></tr><tr><td><a href="/facts/Pseudoephedrine/b2rMjnLv">Pseudoephedrine</a> ((+)-pseudoephedrine)</td><td>224</td><td>1988</td><td>>10000</td><td><a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a></td></tr><tr><td colspan="7">Notes: The smaller the value, the more strongly the substance releases the neurotransmitter. See also <a href="/facts/Monoamine_releasing_agent/JwSvmyR8">Monoamine releasing agent § Activity profiles</a> for a larger table with more compounds.</td></tr></tbody></table> <p>Ephedrine, a <a href="/facts/Sympathomimetic_amine/IEYU5ERW">sympathomimetic amine</a>, acts on part of the <a href="/facts/Sympathetic_nervous_system/hs8psNRd">sympathetic nervous system</a> (SNS). The principal mechanism of action relies on its indirect stimulation of the <a href="/facts/Adrenergic_receptor/uoAeJbcN">adrenergic receptor</a> system by increasing activation of <a href="/facts/%CE%91-adrenergic_receptor/uoAeJbcN">α-</a> and <a href="/facts/%CE%92-adrenergic_receptor/uoAeJbcN">β-adrenergic receptors</a> via <a href="/facts/Norepinephrine_releasing_agent/Ua8s5KKG">induction of norepinephrine release</a>.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> The presence of direct interactions with α-adrenergic receptors is unlikely but still controversial.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a><a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a><a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a><a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> L-ephedrine, and particularly its stereoisomer <a href="/facts/Norpseudoephedrine/jPsMXGhs">norpseudoephedrine</a> (which is also present in <i><a href="/facts/Catha_edulis/2RHjrqgf">Catha edulis</a></i>) has indirect <a href="/facts/Sympathomimetic/IEYU5ERW">sympathomimetic</a> effects and due to its ability to cross the <a href="/facts/Blood%E2%80%93brain_barrier/xYzvVwdu">blood–brain barrier</a>, it is a <a href="/facts/Central_nervous_system/k8I6To97">CNS</a> <a href="/facts/Stimulant/nmBdAXM5">stimulant</a> similar to <a href="/facts/Amphetamine/yKIpLJ9E">amphetamines</a>, but less pronounced, as it releases norepinephrine and <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> in the <a href="/facts/Brain/EKla9NkJ">brain</a>.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> </p> <h3>Pharmacokinetics</h3> <h4>Absorption</h4> <p>The <a href="/facts/Oral_administration/vNQcvLVx">oral</a> <a href="/facts/Bioavailability/9l6na9MV">bioavailability</a> of ephedrine is 88%.<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> The <a href="/facts/Onset_of_action/BTIWvLSY">onset of action</a> of ephedrine orally is 15 to 60 minutes, via <a href="/facts/Intramuscular_injection/PPNwW2wB">intramuscular injection</a> is 10 to 20 minutes, and via <a href="/facts/Intravenous_infusion/AwwuD3Nu">intravenous infusion</a> is within seconds.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> </p> <h4>Distribution</h4> <p>Its <a href="/facts/Plasma_protein_binding/7u7qFYmb">plasma protein binding</a> is approximately 24 to 29%, with 5 to 10% bound to <a href="/facts/Human_serum_albumin/wI8vu5py">albumin</a>.<a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a><a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a><a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a> </p> <h4>Metabolism</h4> <p>Ephedrine is largely not <a href="/facts/Drug_metabolism/I5nQ28Ma">metabolized</a>.<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a> <a href="/facts/Norephedrine/Bp2fDnBs">Norephedrine</a> (phenylpropanolamine) is an <a href="/facts/Active_metabolite/1zbPKbI0">active metabolite</a> of ephedrine formed via <i>N</i>-<a href="/facts/Demethylation/AvM5BLjD">demethylation</a>.<a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a><a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a> About 8 to 20% of an oral dose of ephedrine is demethylated into norephedrine, about 4 to 13% is <a href="/facts/Oxidation/Pyd5RVcj">oxidatively</a> <a href="/facts/Deamination/aBIhMC23">deaminated</a> into <a href="/facts/Benzoic_acid/7HrmrBYS">benzoic acid</a>, and a small fraction is converted into 1,2-dihydroxy-1-phenylpropane.<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a> </p> <h4>Elimination</h4> <p>Ephedrine is <a href="/facts/Elimination_(pharmacology)/E0LubyYL">eliminated</a> mainly in <a href="/facts/Urine/oNUYVtvX">urine</a>, with 60% (range 53–79%) <a href="/facts/Excretion/mspsTfnv">excreted</a> unchanged.<a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a><a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a> </p><p>The <a href="/facts/Elimination_half-life/7nB2JtMr">elimination half-life</a> of ephedrine is 6 hours.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> Its <a href="/facts/Duration_of_action/zdvfFshl">duration of action</a> orally is 2 to 4 hours and via intravenous or intramuscular injection is 60 minutes. </p><p>The elimination of ephedrine is dependent on urinary <a href="/facts/PH/RnSv8D7y">pH</a>.<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a> </p> <h2 id="chemistry">Chemistry</h2> <p>Ephedrine, or (−)-(1<i>R</i>,2<i>S</i>)-ephedrine, also known as (1<i>R</i>,2<i>S</i>)-β-hydroxy-<i>N</i>-methyl-α-methyl-β-phenethylamine or as (1<i>R</i>,2<i>S</i>)-β-hydroxy-<i>N</i>-methylamphetamine, is a <a href="/facts/Substituted_phenethylamine/dte6TQxS">substituted phenethylamine</a> and <a href="/facts/Substituted_amphetamine/KlmrodPb">amphetamine</a> <a href="/facts/Chemical_derivative/JYcbLkbm">derivative</a>. It is similar in <a href="/facts/Chemical_structure/r5rT1Lj4">chemical structure</a> to <a href="/facts/Phenylpropanolamine/Bp2fDnBs">phenylpropanolamine</a>, <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a>, and <a href="/facts/Epinephrine/k7vvMI7E">epinephrine</a> (adrenaline). It differs from methamphetamine only by the presence of a <a href="/facts/Hydroxyl/1Hs2QAEv">hydroxyl</a> group (–OH). Chemically, ephedrine is an <a href="/facts/Alkaloid/m6hUXohz">alkaloid</a> with a <a href="/facts/Phenethylamine/XyjysSul">phenethylamine</a> skeleton found in various plants in the genus <i><a href="/facts/Ephedra_(genus)/P4QTfalE">Ephedra</a></i> (family <a href="/facts/Ephedraceae/P4QTfalE">Ephedraceae</a>). It is most usually marketed as the <a href="/facts/Hydrochloride/7Sdqua4a">hydrochloride</a> or <a href="/facts/Sulfate/yuWVxsUf">sulfate</a> <a href="/facts/Salt_(chemistry)/lsSKwGpn">salt</a>.<a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a> </p><p>It has an experimental <a href="/facts/Partition_coefficient/D4aTlBal">log P</a> of 1.13, while its predicted log P values range from 0.9 to 1.32.<a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a><a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a><a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a> The <a href="/facts/Lipophilicity/AWpsR8Xe">lipophilicity</a> of amphetamines is closely related to their <a href="/facts/Blood%E2%80%93brain_barrier/xYzvVwdu">brain permeability</a>.<a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> For comparison to ephedrine, the experimental log P of <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a> is 2.1,<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a> of <a href="/facts/Amphetamine/yKIpLJ9E">amphetamine</a> is 1.8,<a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a><a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a> of <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a> is 0.89,<a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a> of <a href="/facts/Phenylpropanolamine/Bp2fDnBs">phenylpropanolamine</a> is 0.7,<a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a> of <a href="/facts/Phenylephrine/sf4DxQws">phenylephrine</a> is -0.3,<a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a> and of <a href="/facts/Norepinephrine_(medication)/faPlPMnD">norepinephrine</a> is -1.2.<a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a> Methamphetamine has high brain permeability,<a class="footnote-ref" id="fnref:92" href="#fn:92"><sup>92</sup></a> whereas phenylephrine and norepinephrine are <a href="/facts/Peripherally_selective_drug/Jzzu4aSg">peripherally selective drugs</a>.<a class="footnote-ref" id="fnref:93" href="#fn:93"><sup>93</sup></a><a class="footnote-ref" id="fnref:94" href="#fn:94"><sup>94</sup></a> The optimal log P for brain permeation and central activity is about 2.1 (range 1.5–2.7).<a class="footnote-ref" id="fnref:95" href="#fn:95"><sup>95</sup></a> </p><p>Ephedrine hydrochloride has a melting point of 187−188 °C.<a class="footnote-ref" id="fnref:96" href="#fn:96"><sup>96</sup></a> </p><p>The <a href="/facts/Racemic_mixture/STEagtrD">racemic</a> form of ephedrine is <a href="/facts/Racephedrine/wxXefYXQ">racephedrine</a> ((±)-ephedrine; <i>dl</i>-ephedrine; (1<i>RS</i>,2<i>SR</i>)-ephedrine).<a class="footnote-ref" id="fnref:97" href="#fn:97"><sup>97</sup></a> A <a href="/facts/Stereoisomer/I3kzlDE8">stereoisomer</a> of ephedrine is <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>.<a class="footnote-ref" id="fnref:98" href="#fn:98"><sup>98</sup></a> <a href="/facts/Chemical_derivative/JYcbLkbm">Derivatives</a> of ephedrine include <a href="/facts/Methylephedrine/vaJ5vw3E">methylephedrine</a> (<i>N</i>-methylephedrine), <a href="/facts/Etafedrine/fQnqkpzp">etafedrine</a> (<i>N</i>-ethylephedrine), <a href="/facts/Cinnamedrine/rAlzhhBN">cinnamedrine</a> (<i>N</i>-cinnamylephedrine), and <a href="/facts/Oxilofrine/TWueuLyx">oxilofrine</a> (4-hydroxyephedrine).<a class="footnote-ref" id="fnref:99" href="#fn:99"><sup>99</sup></a> <a href="/facts/Structural_analog/3aysWSVG">Analogues</a> of ephedrine include <a href="/facts/Phenylpropanolamine/Bp2fDnBs">phenylpropanolamine</a> (norephedrine) and <a href="/facts/Metaraminol/ACjP7DCN">metaraminol</a> (3-hydroxynorephedrine).<a class="footnote-ref" id="fnref:100" href="#fn:100"><sup>100</sup></a> </p><p>The presence of an <i>N</i>-<a href="/facts/Methyl_group/fkM97EMD">methyl group</a> decreases binding affinities at α-adrenergic receptors, compared with norephedrine. Ephedrine, though, binds better than <a href="/facts/N-Methylephedrine/S17mBoHo"><i>N</i>-methylephedrine</a>, which has an additional methyl group at the nitrogen atom. Also, the <a href="/facts/Stereochemistry/XkcRVNwd">steric</a> orientation of the hydroxyl group is important for receptor binding and functional activity.<a class="footnote-ref" id="fnref:101" href="#fn:101"><sup>101</sup></a> </p> <h3>Nomenclature</h3> <p>Ephedrine exhibits <a href="/facts/Optical_isomer/p5a9pftB">optical isomerism</a> and has two <a href="/facts/Chirality_(chemistry)/p5a9pftB">chiral</a> centres, giving rise to four <a href="/facts/Stereoisomer/I3kzlDE8">stereoisomers</a>. By convention, the pair of <a href="/facts/Enantiomer/wjPv5J3y">enantiomers</a> with the stereochemistry (1<i>R</i>,2<i>S</i>) and (1<i>S</i>,2<i>R</i>) is designated ephedrine, while the pair of enantiomers with the stereochemistry (1<i>R</i>,2<i>R</i>) and (1<i>S</i>,2<i>S</i>) is called pseudoephedrine. </p><p>The isomer which is marketed is (−)-(1<i>R</i>,2<i>S</i>)-ephedrine.<a class="footnote-ref" id="fnref:102" href="#fn:102"><sup>102</sup></a> </p><p>In the outdated <a href="/facts/Chirality_(chemistry)/p5a9pftB">D/L system</a> (+)-ephedrine is also referred to as D-ephedrine and (−)-ephedrine as L-ephedrine (in which case, in the <a href="/facts/Fischer_projection/SVEblozd">Fischer projection</a>, the <a href="/facts/Phenyl_group/Ql9Yx5uu">phenyl ring</a> is drawn at the bottom).<a class="footnote-ref" id="fnref:103" href="#fn:103"><sup>103</sup></a><a class="footnote-ref" id="fnref:104" href="#fn:104"><sup>104</sup></a> </p><p>Often, the D/L system (with <a href="/facts/Small_caps/SVH5prpT">small caps</a>) and the d/l system (with <a href="/facts/Lower-case/KQcwaUUD">lower-case</a>) are confused. The result is that the levorotary l-ephedrine is wrongly named L-ephedrine and the dextrorotary d-pseudoephedrine (the diastereomer) wrongly D-pseudoephedrine. </p><p>The <a href="/facts/IUPAC_name/qIDqTvoI">IUPAC names</a> of the two enantiomers are (1<i>R</i>,2<i>S</i>)- respectively (1<i>S</i>,2<i>R</i>)-2-methylamino-1-phenylpropan-1-ol. A synonym is <i>erythro</i>-ephedrine. </p> <h3>Detection in body fluids</h3> <p>Ephedrine may be quantified in blood, plasma, or urine to monitor possible abuse by athletes, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Many commercial <a href="/facts/Immunoassay/eHo2YM9S">immunoassay</a> screening tests directed at the amphetamines cross-react appreciably with ephedrine, but chromatographic techniques can easily distinguish ephedrine from other phenethylamine derivatives. Blood or plasma ephedrine concentrations are typically in the 20–200 μg/L range in persons taking the drug therapeutically, 300–3000 μg/L in abusers or poisoned patients, and 3–20 mg/L in cases of acute fatal overdosage. The current <a href="/facts/World_Anti-Doping_Agency/z1KV3bhB">World Anti-Doping Agency</a> (WADA) limit for ephedrine in an athlete's urine is 10 μg/mL.<a class="footnote-ref" id="fnref:105" href="#fn:105"><sup>105</sup></a><a class="footnote-ref" id="fnref:106" href="#fn:106"><sup>106</sup></a><a class="footnote-ref" id="fnref:107" href="#fn:107"><sup>107</sup></a><a class="footnote-ref" id="fnref:108" href="#fn:108"><sup>108</sup></a> </p> <h2 id="history">History</h2> <h3>Asia</h3> <p>Ephedrine in its natural form, known as <a href="/facts/Ephedra_(plant)/P4QTfalE"><i>máhuáng</i></a> (麻黄) in <a href="/facts/Traditional_Chinese_medicine/51rSRXua">traditional Chinese medicine</a>, has been documented in China since the <a href="/facts/Han_dynasty/hanfxS9D">Han dynasty</a> (206 BC – 220 AD) as an <a href="/facts/Asthma/7GkJvxn3">antiasthmatic</a> and stimulant.<a class="footnote-ref" id="fnref:109" href="#fn:109"><sup>109</sup></a> In traditional Chinese medicine, <i>máhuáng</i> has been used as a treatment for asthma and bronchitis for centuries.<a class="footnote-ref" id="fnref:110" href="#fn:110"><sup>110</sup></a> </p><p>In 1885, the chemical synthesis of ephedrine was first accomplished by Japanese <a href="/facts/Organic_chemist/djxhxaNg">organic chemist</a> <a href="/facts/Nagai_Nagayoshi/qNErWcGJ">Nagai Nagayoshi</a> based on his research on <a href="/facts/Japanese_traditional_medicine/lQqKAFFu">traditional Japanese</a> and <a href="/facts/Chinese_herbology/JF2XKnhH">Chinese herbal medicines</a>. </p><p>The industrial manufacture of ephedrine in China began in the 1920s, when <a href="/facts/Merck_%26_Co./8YD8dvwR">Merck</a> began marketing and selling the drug as ephetonin. Ephedrine exports from China to the West grew from 4 to 216 tonnes between 1926 and 1928.<a class="footnote-ref" id="fnref:111" href="#fn:111"><sup>111</sup></a> </p> <h3>Western medicine</h3> <p>Ephedrine was first introduced for medical use in the <a href="/facts/United_States/P0sCdLe5">United States</a> in 1926.<a class="footnote-ref" id="fnref:112" href="#fn:112"><sup>112</sup></a> </p><p>It was introduced in 1948 in <a href="/facts/Vicks/nuUSa5Eu">Vicks</a> Vatronol nose drops (now discontinued) which contained ephedrine sulfate as the active ingredient for rapid nasal decongestion. </p> <h2 id="society-and-culture">Society and culture</h2> <h3>Names</h3> <p><i>Ephedrine</i> is the <a href="/facts/Generic_term/nENLNhIF">generic name</a> of the drug and its <a href="/facts/British_Approved_Name/pm1t52SQ">BAN</a>Tooltip British Approved Name.<a class="footnote-ref" id="fnref:113" href="#fn:113"><sup>113</sup></a><a class="footnote-ref" id="fnref:114" href="#fn:114"><sup>114</sup></a><a class="footnote-ref" id="fnref:115" href="#fn:115"><sup>115</sup></a> Its <a href="/facts/D%C3%A9nomination_Commune_Fran%C3%A7aise/Kvfl1AVE">DCF</a>Tooltip Dénomination Commune Française is <i>ephédrine</i> while its <a href="/facts/Denominazione_Comune_Italiana/wsNJbX1K">DCIT</a>Tooltip Denominazione Comune Italiana is <i>efedrina</i>.<a class="footnote-ref" id="fnref:116" href="#fn:116"><sup>116</sup></a><a class="footnote-ref" id="fnref:117" href="#fn:117"><sup>117</sup></a> In the case of the <a href="/facts/Hydrochloride/7Sdqua4a">hydrochloride</a> <a href="/facts/Salt_(chemistry)/lsSKwGpn">salt</a>, its generic name is <i>ephedrine hydrochloride</i> and this is its <a href="/facts/United_States_Adopted_Name/5AFEKGfQ">USAN</a>Tooltip United States Adopted Name, <a href="/facts/British_Approved_Name/pm1t52SQ">BANM</a>Tooltip British Approved Name, and <a href="/facts/Japanese_Accepted_Name/2TWpxztK">JAN</a>Tooltip Japanese Accepted Name.<a class="footnote-ref" id="fnref:118" href="#fn:118"><sup>118</sup></a><a class="footnote-ref" id="fnref:119" href="#fn:119"><sup>119</sup></a><a class="footnote-ref" id="fnref:120" href="#fn:120"><sup>120</sup></a> In the case of the <a href="/facts/Sulfate/yuWVxsUf">sulfate</a> salt, its generic name is <i>ephedrine sulfate</i> or <i>ephedrine sulphate</i> and the former is its <a href="/facts/United_States_Adopted_Name/5AFEKGfQ">USAN</a>Tooltip United States Adopted Name while the latter is its <a href="/facts/British_Approved_Name/pm1t52SQ">BANM</a>Tooltip British Approved Name.<a class="footnote-ref" id="fnref:121" href="#fn:121"><sup>121</sup></a><a class="footnote-ref" id="fnref:122" href="#fn:122"><sup>122</sup></a><a class="footnote-ref" id="fnref:123" href="#fn:123"><sup>123</sup></a> A synonym of ephedrine sulfate is <i>isofedrol</i>.<a class="footnote-ref" id="fnref:124" href="#fn:124"><sup>124</sup></a> These names all refer to the (1<i>R</i>,2<i>R</i>)-<a href="/facts/Enantiomer/wjPv5J3y">enantiomer</a> of ephedrine.<a class="footnote-ref" id="fnref:125" href="#fn:125"><sup>125</sup></a><a class="footnote-ref" id="fnref:126" href="#fn:126"><sup>126</sup></a> The <a href="/facts/Racemic_mixture/STEagtrD">racemic</a> form of ephedrine is known as <i><a href="/facts/Racephedrine/wxXefYXQ">racephedrine</a></i> and this is its <a href="/facts/International_Nonproprietary_Name/wYL655x6">INN</a>Tooltip International Nonproprietary Name and <a href="/facts/British_Approved_Name/pm1t52SQ">BAN</a>Tooltip British Approved Name, while the hydrochloride salt of the racemic form is <i>racephedrine hydrochloride</i> and this is its <a href="/facts/United_States_Adopted_Name/5AFEKGfQ">USAN</a>Tooltip United States Adopted Name.<a class="footnote-ref" id="fnref:127" href="#fn:127"><sup>127</sup></a> </p> <h3>Recreational use</h3> <p>As a <a href="/facts/Substituted_phenethylamine/dte6TQxS">phenethylamine</a>, ephedrine has a similar chemical structure to <a href="/facts/Substituted_amphetamine/KlmrodPb">amphetamines</a> and is a <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a> <a href="/facts/Structural_analog/3aysWSVG">analog</a> having the methamphetamine structure with a <a href="/facts/Hydroxyl/1Hs2QAEv">hydroxyl</a> group at the <a href="/facts/Phenylethylamine/XyjysSul">β position</a>. Because of ephedrine's structural similarity to methamphetamine, it can be used to create methamphetamine using <a href="/facts/Redox/Pyd5RVcj">chemical reduction</a> in which ephedrine's hydroxyl group is removed; this has made ephedrine a highly sought-after chemical precursor in the <a href="/facts/Clandestine_chemistry/7h0ljKSs">illicit manufacture</a> of <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a>. </p><p>The most popular method for reducing ephedrine to methamphetamine is similar to the <a href="/facts/Birch_reduction/0VPY857Y">Birch reduction</a>, in that it uses <a href="/facts/Anhydrous_ammonia/MtLtJFtz">anhydrous ammonia</a> and <a href="/facts/Lithium/7vXX6BWA">lithium</a> metal in the reaction. The second-most popular method uses red <a href="/facts/Phosphorus/27xCeIqs">phosphorus</a> and <a href="/facts/Iodine/JlfMecMf">iodine</a> in the reaction with ephedrine. Moreover, ephedrine can be synthesized into <a href="/facts/Methcathinone/tF4VcbcI">methcathinone</a> via simple <a href="/facts/Oxidation/Pyd5RVcj">oxidation</a>. As such, ephedrine is listed as a table-I precursor under the <i><a href="/facts/United_Nations_Convention_Against_Illicit_Traffic_in_Narcotic_Drugs_and_Psychotropic_Substances/DIes6dB8">United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances</a></i>.<a class="footnote-ref" id="fnref:128" href="#fn:128"><sup>128</sup></a> </p> <h3>Use in exercise and sports</h3> <p>Ephedrine has been used as a <a href="/facts/Performance-enhancing_drug/NydFWSGJ">performance-enhancing drug</a> in <a href="/facts/Exercise/egYQjt8A">exercise</a> and <a href="/facts/Sports/0NazHJMC">sports</a>.<a class="footnote-ref" id="fnref:129" href="#fn:129"><sup>129</sup></a><a class="footnote-ref" id="fnref:130" href="#fn:130"><sup>130</sup></a><a class="footnote-ref" id="fnref:131" href="#fn:131"><sup>131</sup></a><a class="footnote-ref" id="fnref:132" href="#fn:132"><sup>132</sup></a> It can increase <a href="/facts/Heart_rate/YngB0bzg">heart rate</a>, <a href="/facts/Blood_pressure/VtqqSM2J">blood pressure</a>, and <a href="/facts/Cardiac_contractility/0BdQPIsv">cardiac contractility</a> as well as act as a <a href="/facts/Psychostimulant/nmBdAXM5">psychostimulant</a>.<a class="footnote-ref" id="fnref:133" href="#fn:133"><sup>133</sup></a> Ephedrine is often used in combination with <a href="/facts/Caffeine/Hx6E2QC5">caffeine</a> for performance-enhancing purposes.<a class="footnote-ref" id="fnref:134" href="#fn:134"><sup>134</sup></a><a class="footnote-ref" id="fnref:135" href="#fn:135"><sup>135</sup></a> </p> <h3>Other uses</h3> <p>In <a href="/facts/Chemical_synthesis/3KXsVVwC">chemical synthesis</a>, ephedrine is used in bulk quantities as a <a href="/facts/Chiral_auxiliary/bn9wa27M">chiral auxiliary</a> group.<a class="footnote-ref" id="fnref:136" href="#fn:136"><sup>136</sup></a> </p> <p>In <a href="/facts/Saquinavir/0v9eGp2l">saquinavir</a> synthesis, the half-acid is resolved as its salt with l-ephedrine. </p> <h3>Legal status</h3> <h4>Canada</h4> <p>In January 2002, <a href="/facts/Health_Canada/BV8TuL14">Health Canada</a> issued a voluntary recall of all ephedrine products containing more than 8 mg per dose, all combinations of ephedrine with other stimulants such as caffeine, and all ephedrine products marketed for weight-loss or bodybuilding indications, citing a serious risk to health.<a class="footnote-ref" id="fnref:137" href="#fn:137"><sup>137</sup></a> Ephedrine is still sold as an oral nasal decongestant<a class="footnote-ref" id="fnref:138" href="#fn:138"><sup>138</sup></a> in 8 mg pills as a natural health product, with a limit of 0.4 g (400 mg) per package, the limit established by the Controlled Drugs and Substances Act as it is considered as Class A Precursor.<a class="footnote-ref" id="fnref:139" href="#fn:139"><sup>139</sup></a> </p> <h4>United States</h4> <p>In 1997, the <a href="/facts/Food_and_Drug_Administration/rCEnh9WB">FDA</a> proposed a regulation on ephedra (the herb from which ephedrine is obtained), which limited an ephedra dose to 8 mg (of active ephedrine) with no more than 24 mg per day.<a class="footnote-ref" id="fnref:140" href="#fn:140"><sup>140</sup></a> This proposed rule was withdrawn, in part, in 2000 because of "concerns regarding the agency's basis for proposing a certain dietary ingredient level and a duration of use limit for these products."<a class="footnote-ref" id="fnref:141" href="#fn:141"><sup>141</sup></a> In 2004, the FDA created a ban on ephedrine alkaloids marketed for reasons other than asthma, colds, allergies, other disease, or traditional Asian use.<a class="footnote-ref" id="fnref:142" href="#fn:142"><sup>142</sup></a> On April 14, 2005, the <a href="/facts/United_States_District_Court_for_the_District_of_Utah/c1dAJsdk">U.S. District Court for the District of Utah</a> ruled the FDA did not have proper evidence that low dosages of ephedrine alkaloids are actually unsafe,<a class="footnote-ref" id="fnref:143" href="#fn:143"><sup>143</sup></a> but on August 17, 2006, the <a href="/facts/United_States_Court_of_Appeals_for_the_Tenth_Circuit/llRnEUfX">U.S. Court of Appeals for the Tenth Circuit</a> in Denver upheld the FDA's final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States.<a class="footnote-ref" id="fnref:144" href="#fn:144"><sup>144</sup></a> Furthermore, ephedrine is banned by the NCAA, MLB, NFL, and PGA.<a class="footnote-ref" id="fnref:145" href="#fn:145"><sup>145</sup></a> Ephedrine is, however, still legal in many applications outside of dietary supplements. Purchasing is currently limited and monitored, with specifics varying from state to state. </p><p>The <a href="/facts/United_States_House_of_Representatives/cdBPb9pY">House</a> passed the <a href="/facts/Combat_Methamphetamine_Epidemic_Act_of_2005/b4C3X3Xw">Combat Methamphetamine Epidemic Act of 2005</a> as an amendment to the renewal of the <a href="/facts/USA_PATRIOT_Act/EuM6gPJ6">USA PATRIOT Act</a>. Signed into law by President <a href="/facts/George_W._Bush/mYSgM515">George W. Bush</a> on March 6, 2006, the act amended the <a href="/facts/US_Code/2AjxEDPq">US Code</a> (21 USC 830) concerning the sale of products containing ephedrine and the closely related drug <a href="/facts/Pseudoephedrine/b2rMjnLv">pseudoephedrine</a>. Both substances are used as <a href="/facts/Drug_precursors/e2tzKg7G">precursors</a> in the <a href="/facts/Clandestine_chemistry/7h0ljKSs">illicit production</a> of <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a>, and to discourage that use the federal statute included the following requirements for merchants who sell these products: </p> <ul><li>A retrievable record of all purchases identifying the name and address of each party to be kept for two years</li> <li>Required verification of proof of identity of all purchasers</li> <li>Required protection and disclosure methods in the collection of personal information</li> <li>Reports to the <a href="/facts/United_States_Attorney_General/8VaY1rlI">Attorney General</a> of any suspicious payments or disappearances of the regulated products</li> <li>Non-liquid dose form of regulated product may only be sold in unit-dose blister packs</li> <li>Regulated products are to be sold behind the counter or in a locked cabinet in such a way as to restrict access</li> <li>Daily sales of regulated products not to exceed 3.6 g to a single purchaser, without regard to the number of transactions</li> <li>Monthly sales to a single purchaser not to exceed 9 g of pseudoephedrine base in regulated products</li></ul> <p>The law gives similar regulations to mail-order purchases, except the monthly sales limit is 7.5 g. </p><p>As a pure herb or tea, <i>má huáng</i>, containing ephedrine, is still sold legally in the US. The law restricts/prohibits its being sold as a dietary supplement (pill) or as an ingredient/additive to other products, like diet pills. </p> <h4>Australia</h4> <p>Ephedrine and all <i>Ephedra</i> species that contain it are considered Schedule 4 substances under the <a href="/facts/Standard_for_the_Uniform_Scheduling_of_Medicines_and_Poisons/Lna99E1T">Poisons Standard</a>. A Schedule 4 drug is considered a Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription under the <a href="/facts/Standard_for_the_Uniform_Scheduling_of_Medicines_and_Poisons/Lna99E1T">Poisons Standard</a>. </p> <h4>South Africa</h4> <p>In South Africa, ephedrine was moved to schedule 6 on 27 May 2008,<a class="footnote-ref" id="fnref:146" href="#fn:146"><sup>146</sup></a> which makes pure ephedrine tablets prescription only. Pills containing ephedrine up to 30 mg per tablet in combination with other medications are still available OTC, schedule 1 and 2, for sinus, head colds, and influenza. </p> <h4>Germany</h4> <p>Ephedrine was freely available in pharmacies in Germany until 2001. Afterward, access was restricted since it was mostly bought for unindicated uses. Similarly, ephedra can only be bought with a prescription. Since April 2006, all products, including plant parts, that contain ephedrine are only available with a prescription.<a class="footnote-ref" id="fnref:147" href="#fn:147"><sup>147</sup></a> </p> <h2 id="sources">Sources</h2> <h3>Agricultural</h3> <p>Ephedrine is obtained from the plant <i><a href="/facts/Ephedra_sinica/3k9HqhD0">Ephedra sinica</a></i> and other members of the genus <i><a href="/facts/Ephedra_(plant)/P4QTfalE">Ephedra</a>,</i> from which the name of the substance is derived. Raw materials for the manufacture of ephedrine and traditional Chinese medicines are produced in China on a large scale. As of 2007, companies produced for export US$13 million worth of ephedrine from 30,000 tons of ephedra annually, or about ten times the amount used in traditional Chinese medicine.<a class="footnote-ref" id="fnref:148" href="#fn:148"><sup>148</sup></a> </p> <h3>Synthetic</h3> <p>Most of the l-ephedrine produced today for official medical use is made synthetically as the extraction and isolation process from <i>E. sinica</i> is tedious and no longer cost-effective.<a class="footnote-ref" id="fnref:149" href="#fn:149"><sup>149</sup></a>[<i>unreliable source?</i>] </p> <h3>Biosynthetic</h3> <p>Ephedrine was long thought to come from modifying the amino acid L-phenylalanine.<a class="footnote-ref" id="fnref:150" href="#fn:150"><sup>150</sup></a> L-Phenylalanine would be decarboxylated and subsequently attacked with ω-aminoacetophenone. Methylation of this product would then produce ephedrine. This pathway has since been disproven.<a class="footnote-ref" id="fnref:151" href="#fn:151"><sup>151</sup></a> A new pathway proposed suggests that phenylalanine first forms <a href="/facts/Cinnamoyl-CoA/2CxHGncw">cinnamoyl-CoA</a> via the enzymes <a href="/facts/Phenylalanine_ammonia-lyase/qaAokxQA">phenylalanine ammonia-lyase</a> and acyl CoA ligase.<a class="footnote-ref" id="fnref:152" href="#fn:152"><sup>152</sup></a> The cinnamoyl-CoA is then reacted with a hydratase to attach the alcohol functional group. The product is then reacted with a retro-aldolase, forming <a href="/facts/Benzaldehyde/GyboW1KC">benzaldehyde</a>. Benzaldehyde reacts with <a href="/facts/Pyruvic_acid/qJTgl4J9">pyruvic acid</a> to attach a 2-carbon unit. This product then undergoes transamination and methylation to form ephedrine and its stereoisomer, pseudoephedrine.<a class="footnote-ref" id="fnref:153" href="#fn:153"><sup>153</sup></a> </p> <h2 id="external-links">External links</h2> Wikimedia Commons has media related to L-Ephedrine. <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Ephedrine". The American Society of Health-System Pharmacists. Archived from the original on 2017-09-09. Retrieved 8 September 2017. <a href="https://www.drugs.com/monograph/ephedrine.html" target="_blank">https://www.drugs.com/monograph/ephedrine.html</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Ephedrine". The American Society of Health-System Pharmacists. Archived from the original on 2017-09-09. 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