{{Short description|Chemical compound}} {{Distinguish|Caffeine}} {{Drugbox | Verifiedfields = changed | class = {{Plainlist| *Appetite suppressant *{{abbr|CNS|Central nervous system}} stimulant *Norepinephrine-dopamine releasing agent }} | solubility = 20 | verifiedrevid = 446197235 | IUPAC_name = (1''S'',2''S'')-2-amino-1-phenylpropan-1-ol | image = Cathine structure.svg | image_class = skin-invert-image | width = 200px
<!--Clinical data-->| tradename = | MedlinePlus = | licence_EU = | licence_US = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = S4 | legal_BR = A3 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}</ref> | legal_CA = Schedule IV | legal_DE = Rx-only/Anlage III | legal_US = Schedule IV | legal_UK = Class C | legal_UN = P III | legal_status = | routes_of_administration = Oral
<!--Pharmacokinetic data-->| bioavailability = | metabolism = | elimination_half-life = 1.8–8.6 hours<ref>{{cite journal | vauthors = Toennes SW, Harder S, Schramm M, Niess C, Kauert GF | title = Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves | journal = British Journal of Clinical Pharmacology | volume = 56 | issue = 1 | pages = 125–30 | date = July 2003 | pmid = 12848785 | pmc = 1884326 | doi = 10.1046/j.1365-2125.2003.01834.x }}</ref>
<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 492-39-7 | ATC_prefix = A08 | ATC_suffix = AA07 | PubChem = 441457 | ChEMBL_Ref = {{ebicite|changed|EBI}} | synonyms = {{Plainlist| *(+)-Norpseudoephedrine *Cathine *(1''S'',2''S'')-β-Hydroxyamphetamine }} | ChEMBL = 1412041 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01486 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 390189 | ChEBI = 4109 | KEGG = D07627 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = E1L4ZW2F8O
<!--Chemical data-->| C = 9 | H = 13 | N = 1 | O = 1 | smiles = O[C@@H](c1ccccc1)[C@@H](N)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C9H13NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9,11H,10H2,1H3/t7-,9+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DLNKOYKMWOXYQA-IONNQARKSA-N }}
'''Cathine''', also known as '''{{Small|D}}-norpseudoephedrine''' or as '''(+)-norpseudoephedrine''', is a psychoactive drug of the phenethylamine and amphetamine groups which acts as a stimulant. Along with cathinone, it is found naturally in ''Catha edulis'' (khat), and contributes to the overall effects of the plant.<ref name="behav2010">{{cite journal | vauthors = Hoffman R, Al'Absi M | title = Khat use and neurobehavioral functions: suggestions for future studies | journal = Journal of Ethnopharmacology | volume = 132 | issue = 3 | pages = 554–63 | date = December 2010 | pmid = 20553832 | pmc = 2976806 | doi = 10.1016/j.jep.2010.05.033 }}</ref> Cathine has approximately 7 to 10% of the potency of amphetamine.<ref name = behav2010/>
==Pharmacology== Like amphetamines, cathinone and ephedrine, cathine acts as a norepinephrine releasing agent (NRA).<ref name = behav2010/> It also acts as a dopamine releasing agent (DRA).<ref name = behav2010/><ref>{{cite journal | vauthors = Kalyanasundar B, Perez CI, Arroyo B, Moreno MG, Gutierrez R | title = The Appetite Suppressant D-norpseudoephedrine (Cathine) Acts ''via'' D1/D2-Like Dopamine Receptors in the Nucleus Accumbens Shell | journal = Frontiers in Neuroscience | volume = 14 | article-number = 572328 | date = 2020-10-16 | pmid = 33177980 | pmc = 7596745 | doi = 10.3389/fnins.2020.572328 | doi-access = free }}</ref>
{| class="wikitable" style="font-size:small;" |+ {{Nowrap|Monoamine release by cathine and related agents ({{Abbrlink|EC<sub>50</sub>|half maximal effective concentration}}, nM)}} |- ! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref |- | Dextroamphetamine (''S''(+)-amphetamine) || 6.6–7.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref> |- | ''S''(–)-Cathinone || 12.4 || 18.5 || 2,366 || <ref name="RothmanVuPartilla2003">{{cite journal | vauthors = Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA | title = In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates | journal = J Pharmacol Exp Ther | volume = 307 | issue = 1 | pages = 138–145 | date = October 2003 | pmid = 12954796 | doi = 10.1124/jpet.103.053975 | url = }}</ref> |- | Ephedrine ((–)-ephedrine) || 43.1–72.4 || 236–1,350 || >10,000 || <ref name="RothmanBaumannDersch2001" /> |- | (+)-Ephedrine || 218 || 2,104 || >10,000 || <ref name="RothmanBaumannDersch2001" /><ref name="RothmanVuPartilla2003" /> |- | Dextromethamphetamine (''S''(+)-methamphetamine) || 12.3–13.8 || 8.5–24.5 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–203 | date = April 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 | url = }}</ref> |- | Levomethamphetamine (''R''(–)-methamphetamine) || 28.5 || 416 || 4,640 || <ref name="RothmanBaumannDersch2001" /> |- | (+)-Phenylpropanolamine ((+)-norephedrine) || 42.1 || 302 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | (–)-Phenylpropanolamine ((–)-norephedrine) || 137 || 1,371 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | Cathine ((+)-norpseudoephedrine) || 15.0 || 68.3 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | (–)-Norpseudoephedrine || 30.1 || 294 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | (–)-Pseudoephedrine || 4,092 || 9,125 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | Pseudoephedrine ((+)-pseudoephedrine) || 224 || 1,988 || >10,000 || <ref name="RothmanVuPartilla2003" /> |- | colspan="5" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. '''Refs:'''<ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur. J. Pharmacol. | volume = 479 | issue = 1–3 | pages = 23–40 | year = 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054}}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Curr Top Med Chem | volume = 6 | issue = 17 | pages = 1845–1859 | date = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = }}</ref> |}
==Chemistry== Cathine is one of the four stereoisomers of phenylpropanolamine (PPA).
==Regulation== The World Anti-Doping Agency's list of prohibited substances (used for the Olympic Games among other athletic events) bans cathine in concentrations of over 5 micrograms per milliliter in urine. Cathine is a Schedule III drug under the Convention on Psychotropic Substances.<ref name="List of controlled substances" /> In the United States, it is classified as a Schedule IV controlled substance.<ref>{{cite web | title = Scheduling Actions | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/a_sched_alpha.pdf | work = Diversion Control Division | publisher = U.S. Department Of Justice, Drug Enforcement Administration (DEA) }}</ref>
In Australia, Cathine is officially a schedule 4 drug prescription only, but is not available or approved for any medical use.
[[File:Catha edulis.jpg|thumb|250px|left|Cathine is found in the shrub khat (''Catha edulis'').]]
In Hong Kong, cathine is regulated under Schedule 1 of Hong Kong's Chapter 134 ''Dangerous Drugs Ordinance''. Unlawful possession is punishable by severe fines and imprisonment.
==Pregnancy== Ephedra, found in many ''Ephedraceae'' species, is a Chinese and Western herb that contains, among other amphetamines, {{sc|D}}-norpseudoephedrine. In the National Birth Defects Prevention Study, which included 18,438 women from 10 states from 1999 to 2003, 1.3% of women reported using ephedra during pregnancy. During the trial, five cases of anencephaly were born to women who used ephedra, however there was no statistically significant association to women not using ephedra (odds ratio 2.8, confidence interval 1.0–7.3).<ref>{{cite journal | vauthors = Smid MC, Metz TD, Gordon AJ | title = Stimulant Use in Pregnancy: An Under-recognized Epidemic Among Pregnant Women | journal = Clinical Obstetrics and Gynecology | volume = 62 | issue = 1 | pages = 168–184 | date = March 2019 | pmid = 30601144 | pmc = 6438363 | doi = 10.1097/GRF.0000000000000418 }}</ref>
A small study of 642 participants in Yemen found that among pregnant women who chewed khat (containing {{sc|D}}-norpseudoephedrine) there was no increased risk of stillbirth or congenital malformations.<ref>{{cite journal | vauthors = Nakajima M, Jebena MG, Taha M, Tesfaye M, Gudina E, Lemieux A, Hoffman R, al'Absi M | display-authors = 6 | title = Correlates of khat use during pregnancy: A cross-sectional study | journal = Addictive Behaviors | volume = 73 | pages = 178–184 | date = October 2017 | pmid = 28531823 | doi = 10.1016/j.addbeh.2017.05.008 }}</ref> Among lactating women who chew khat, {{sc|D}}-norpseudoephedrine is found in breastmilk.<ref>{{cite journal | vauthors = Kristiansson B, Abdul Ghani N, Eriksson M, Garle M, Qirbi A | title = Use of khat in lactating women: a pilot study on breast-milk secretion | journal = Journal of Ethnopharmacology | volume = 21 | issue = 1 | pages = 85–90 | date = September 1987 | pmid = 3695559 | doi = 10.1016/0378-8741(87)90097-3 }}</ref>
==See also== * {{sc|L}}-Norpseudoephedrine, the enantiomer * Methcathinone * ''Ephedra sinica'' ("Ephedra") * Ephedrine * Pseudoephedrine * Methamphetamine
==References== {{Reflist|refs= <ref name="List of controlled substances"> {{cite web | url = http://www.incb.org/pdf/e/list/green.pdf | archive-url = https://web.archive.org/web/20120831222336/http://www.incb.org/pdf/e/list/green.pdf | archive-date = 2012-08-31 | title = List of psychotropic substances under international control | work = International Narcotics Control Board }}</ref>}}
{{Stimulants}} {{Decongestants}} {{Anorectics}} {{Monoamine releasing agents}} {{Phenethylamines}} {{Chemical classes of psychoactive drugs}}
Category:Amphetamine alkaloids Category:Beta-Hydroxyamphetamines Category:Decongestants Category:Euphoriants Category:Methamphetamines Category:Norepinephrine-dopamine releasing agents Category:Recreational drug metabolites Category:Human drug metabolites