View source for Cathine

{{Short description|Chemical compound}}
{{Distinguish|Caffeine}}
{{Drugbox
| Verifiedfields = changed
| class = {{Plainlist|
*[[Appetite suppressant]]
*[[CNS stimulant|{{abbr|CNS|Central nervous system}} stimulant]]
}}
| solubility = 20
| verifiedrevid = 446197235
| type = 
| IUPAC_name = (1''S'',2''S'')-2-amino-1-phenylpropan-1-ol
| image = Cathine2DCSD.svg
| image_class = skin-invert-image
| width = 150px
| alt = 
| caption = 
| width2 = 250px

<!--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 [[substituted phenethylamine|phenethylamine]] and [[substituted amphetamine|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 (pharmacology)|potency]] of [[amphetamine]].<ref name = behav2010/>

==Pharmacology==
Like [[amphetamine]]s, 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>
|-
| [[Cathinone|''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|(+)-Phenylpropanolamine]] ((+)-norephedrine) || 42.1 || 302 || >10,000 || <ref name="RothmanVuPartilla2003" />
|-
| [[Phenylpropanolamine|(–)-Phenylpropanolamine]] ((–)-norephedrine) || 137 || 1,371 || >10,000 || <ref name="RothmanVuPartilla2003" />
|-
| [[Cathine]] ((+)-norpseudoephedrine) || 15.0 || 68.3 || >10,000 || <ref name="RothmanVuPartilla2003" />
|-
| [[L-Norpseudoephedrine|(–)-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:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The [[bioassay|assay]]s were done in rat brain [[synaptosome]]s and human [[potency (pharmacology)|potencies]] may be different. See also [[Monoamine releasing agent#Activity profiles|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 [[Stereoisomerism|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 [[microgram]]s per [[milliliter]] in [[urine]]. Cathine is a [[Convention on Psychotropic Substances#Schedules of Controlled Substances|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 [[Standard for the Uniform Scheduling of Medicines and Poisons|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 (medicine)|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]] [[Statistical association|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 [[Birth defect|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==
* [[L-Norpseudoephedrine|{{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]]