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| =='''What is {{PAGENAME}}?'''==
| | (+)-CPCA, also known as (+)-cis-3-phenylcyclopropylamine, is a chemical compound that acts as a monoamine oxidase inhibitor (MAOI). It is primarily of interest in the field of [[neuropharmacology]] due to its potential effects on [[neurotransmitter]] systems. |
| * It is a stimulant drug similar in structure to pethidine (an opioid that possesses NDRI actions) and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.
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| * '''Synonyms''':
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| # ''[[Nocaine]]''
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| # ''[[263769-22-8]]''
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| # ''[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidine-3-carboxylic acid methyl ester]]''
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| # ''[[CHEMBL296019]]''
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| # ''[[4-(4-Chloro-phenyl)-1-methyl-piperidine-3-carboxylic acid methyl ester]]''
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| # ''[[Methyl (3R,4S)-4-(4-chlorophenyl)-1-methylpiperidine-3-carboxylate]]''
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| # ''[[TL8002108]]''
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| # ''[[SCHEMBL1086468]]''
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| # ''[[DTXSID80180975]]''
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| # ''[[3alpha-Carbomethoxy-4beta-(4-chlorophenyl)-N-methylpiperidine]]''
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| # ''[[ZINC4423541]]''
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| # ''[[BDBM50099288]]''
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| # ''[[MFCD09835335]]''
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| # ''[[PDSP1_001293]]''
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| # ''[[PDSP2_001277]]''
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| # ''[[(+)-Methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate]]''
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| # ''[[769C228]]''
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| # ''[[Q4540627]]''
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| # ''[[(3R,4S)-4-(4-Chloro-phenyl)-1-methylpiperidine-3-carboxylic acid(OMe)]]''
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| # ''[[(1S)-1alpha-Methyl-4beta-(4-chlorophenyl)piperidine-3alpha-carboxylic acid methyl ester]]''
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| # ''[[(3R,4S)-4-(4-Chloro-phenyl)-1-methyl-piperidine-3-carboxylic acid methyl ester]]''
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| # ''[[1-Methyl-4beta-(4-chlorophenyl)piperidine-3alpha-carboxylic acid methyl ester]]''
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| * Molecular Weight: ''267.75''
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| [[File:(+)-CPCA.svg|thumb|(+)-CPCA]]
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| =='''How does this drug work?'''== | | ==Chemical Structure== |
| Like cocaine, (–)-cis-CPCA and (+)-CPCA bind to the [[dopamine transporter]] and inhibit [[dopamine]] uptake, stimulate motor activity in rodents and completely substitute for cocaine in discrimination tests. Pretreatment with (–)-cis-CPCA or (+)-CPCA enhances the cocaine discriminative stimulus in rats. However, there are a number of differences; the locomotor stimulant effects of the piperidine derivatives are much less than those induced by cocaine, and pretreating mice with (–)-cis-CPCA or (+)-CPCA does not increase cocaine induced convulsions, and actually reduced cocaine induced locomotor stimulation. The (–)-cis-CPCA isomer has similar reinforcing effects to cocaine as shown by fixed-ratio self-administration tests in rats, but (+)-CPCA has a flat dose-response curve, and similarly while (–)-cis-CPCA and cocaine had nearly identical break points in a "punished responding" (?) self-administration test, (+)-CPCA had a lower break point than either of the other drugs.
| | (+)-CPCA is a cyclopropylamine derivative, characterized by a three-membered cyclopropane ring attached to a phenyl group. The chemical formula is C9H11N, and it has a molecular weight of 133.19 g/mol. |
| {| class="wikitable"
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| |colspan=4|''Monoamine Reuptake Activity (nM)''
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| |-
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| |'''Compound'''||'''[{{sup|3}}H]NE'''||['''{{sup|3}}H]5-HT'''||['''{{sup|3}}H]DA'''
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| |Cocaine||119||177||275
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| |-
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| |(–)-cis-CPCA||98||390||67
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| |-
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| |(+)-CPCA||90||5900||276
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| |-
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| |}
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| The generally lower efficacy of (+)-CPCA in locomotor and methamphetamine discrimination tests could result from the differential selectivity of the two isomers for the DAT relative to the SERT. That is, if serotonin receptor activation is requisite for maximal efficacy, the difference SERT affinity between (–)-cis-CPCA and (+)-CPCA might play a contributory role in accounting for the differences in the observed pharmacology. Catecholamine selective drugs, like TMP (methylphenidate), are reported to possess decent abuse potential though, so it is not easy to gauge why (+)-CPCA does not entice a strong self-administration propensity. | |
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| A possible explanation might be nocaine preferentially binds to the ↓ DAT, in which case it would be expected to behave somewhat differently from cocaine.<ref name="Lomenzo"/> Some sort of cholinergic effect might also be aversive. For example, muscarinic activity of benztropine analogs is known to limit their reinforcing potential.<ref>{{cite journal | vauthors = Zou MF, Cao J, Kopajtic T, Desai RI, Katz JL, Newman AH | title = Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 21 | pages = 6391–9 | date = October 2006 | pmid = 17034144 | doi = 10.1021/jm060762q }}</ref> Ion-channel activity is another factor that can be used to explain certain differences in pharmacology.
| | ==Mechanism of Action== |
| | As a monoamine oxidase inhibitor, (+)-CPCA functions by inhibiting the activity of the [[monoamine oxidase]] enzyme. This enzyme is responsible for the breakdown of monoamines, which are neurotransmitters such as [[serotonin]], [[dopamine]], and [[norepinephrine]]. By inhibiting this enzyme, (+)-CPCA increases the levels of these neurotransmitters in the brain, potentially affecting mood and behavior. |
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| It is possible that [[sigma receptor]] activity might also account for some of the differences between cocaine and these piperidine mimics (R. Matsumoto, et al. 2001,<ref>{{cite journal | vauthors = Matsumoto RR, Hewett KL, Pouw B, Bowen WD, Husbands SM, Cao JJ, Newman AH | s2cid = 44328858 | title = Rimcazole analogs attenuate the convulsive effects of cocaine: correlation with binding to sigma receptors rather than dopamine transporters | journal = Neuropharmacology | volume = 41 | issue = 7 | pages = 878–86 | date = December 2001 | pmid = 11684152 | doi = 10.1016/S0028-3908(01)00116-2 }}</ref><ref>{{cite journal | vauthors = Matsumoto RR, McCracken KA, Friedman MJ, Pouw B, De Costa BR, Bowen WD | title = Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice | journal = European Journal of Pharmacology | volume = 419 | issue = 2–3 | pages = 163–74 | date = May 2001 | pmid = 11426838 | doi = 10.1016/S0014-2999(01)00968-2 }}</ref><ref>{{cite journal | vauthors = Matsumoto RR, McCracken KA, Pouw B, Zhang Y, Bowen WD | s2cid = 34846910 | title = Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides | journal = Neuropharmacology | volume = 42 | issue = 8 | pages = 1043–55 | date = June 2002 | pmid = 12128006 | doi = 10.1016/S0028-3908(02)00056-4 }}</ref><ref>{{cite journal | vauthors = Matsumoto RR, Liu Y, Lerner M, Howard EW, Brackett DJ | title = Sigma receptors: potential medications development target for anti-cocaine agents | journal = European Journal of Pharmacology | volume = 469 | issue = 1–3 | pages = 1–12 | date = May 2003 | pmid = 12782179 | doi = 10.1016/S0014-2999(03)01723-0 }}</ref> (Ping and Teruo, 2003 rev).<ref>{{cite journal | vauthors = Su TP, Hayashi T | title = Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction | journal = Current Medicinal Chemistry | volume = 10 | issue = 20 | pages = 2073–80 | date = October 2003 | pmid = 12871086 | doi = 10.2174/0929867033456783 | url = https://zenodo.org/record/1235850 }}</ref> Sigma receptors are not specific to cocaine, other psychostimulants like methylphenidate, methamphetamine (E. Nguyen, et al. 2005),<ref>{{cite journal | vauthors = Nguyen EC, McCracken KA, Liu Y, Pouw B, Matsumoto RR | s2cid = 41068558 | title = Involvement of sigma (sigma) receptors in the acute actions of methamphetamine: receptor binding and behavioral studies | journal = Neuropharmacology | volume = 49 | issue = 5 | pages = 638–45 | date = October 2005 | pmid = 15939443 | doi = 10.1016/j.neuropharm.2005.04.016 }}</ref> and phencyclidine are also linked to this neural target. An increased understanding of this receptor recently led to a novel AD being reported that is based around its pharmacology.<ref>{{cite journal | vauthors = Wang J, Mack AL, Coop A, Matsumoto RR | title = Novel sigma (sigma) receptor agonists produce antidepressant-like effects in mice | journal = European Neuropsychopharmacology | volume = 17 | issue = 11 | pages = 708–16 | date = November 2007 | pmid = 17376658 | pmc = 4041597 | doi = 10.1016/j.euroneuro.2007.02.007 }}</ref>
| | ==Potential Applications== |
| | Research into (+)-CPCA has primarily focused on its potential use in treating [[depression]] and other mood disorders. By increasing the availability of monoamines, it may help alleviate symptoms associated with these conditions. However, its use is limited by the potential for side effects and interactions with other medications. |
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| In summary, (+)-CPCA has lower potency and efficacy than cocaine in increasing locomotor activity in rodents. (+)-CPCA only manages to produce partial methamphetamine-like discriminative stimulus effects, although it is fully cocaine-like in cocaine-trained animals. (+)-CPCA has lower reinforcing potential than cocaine as assessed by fixed and progressive ratio IV self-administration tests in rats, with its reinforcing effects confirmed by rhesus monkeys. Furthermore, (+)-CPCA dose dependently antagonizes cocaine-induced locomotion and potentiates the discriminative stimulus effects of a low dose of cocaine. (+)-CPCA, unlike cocaine, does not enhance cocaine-induced convulsions. These results suggest that (+)-CPCA completely mimics certain behavioral actions of cocaine, whereas acting like a weak partial agonist in others, including its ability to attenuate cocaine-induced increase in locomotion and to serve as a positive reinforcing agent in rodents. Thus, (+)-CPCA may have potential utility in the treatment of cocaine addiction, and also offer valuable pharmacological information, furthering our understanding of cocaine's mechanism of action, because it exhibits fundamental differences from other related DARI molecules.
| | ==Side Effects and Risks== |
| | The use of MAOIs, including (+)-CPCA, can lead to several side effects. Common side effects include dizziness, headache, and insomnia. More serious risks involve hypertensive crises, especially when combined with certain foods or other medications that increase monoamine levels. |
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| ==References== | | ==Research and Development== |
| {{reflist}}
| | While (+)-CPCA has shown promise in preclinical studies, further research is needed to fully understand its efficacy and safety profile. Clinical trials are necessary to determine its potential as a therapeutic agent. |
| | | {{nt}} |
| {{Stimulants}}
| | [[Category:Monoamine oxidase inhibitors]] |
| {{Dopaminergics}}
| | [[Category:Neuropharmacology]] |
| {{pharma-stub}}
| | [[Category:Experimental drugs]] |
| {{adapted}} | | <gallery> |
| [[Category:Stimulants]] | | File:(+)-CPCA.svg|(+)-CPCA |
| [[Category:Chloroarenes]] | | </gallery> |
| [[Category:4-Phenylpiperidines]] | |
| [[Category:Carboxylate esters]]
| |
(+)-CPCA, also known as (+)-cis-3-phenylcyclopropylamine, is a chemical compound that acts as a monoamine oxidase inhibitor (MAOI). It is primarily of interest in the field of neuropharmacology due to its potential effects on neurotransmitter systems.
Chemical Structure[edit]
(+)-CPCA is a cyclopropylamine derivative, characterized by a three-membered cyclopropane ring attached to a phenyl group. The chemical formula is C9H11N, and it has a molecular weight of 133.19 g/mol.
Mechanism of Action[edit]
As a monoamine oxidase inhibitor, (+)-CPCA functions by inhibiting the activity of the monoamine oxidase enzyme. This enzyme is responsible for the breakdown of monoamines, which are neurotransmitters such as serotonin, dopamine, and norepinephrine. By inhibiting this enzyme, (+)-CPCA increases the levels of these neurotransmitters in the brain, potentially affecting mood and behavior.
Potential Applications[edit]
Research into (+)-CPCA has primarily focused on its potential use in treating depression and other mood disorders. By increasing the availability of monoamines, it may help alleviate symptoms associated with these conditions. However, its use is limited by the potential for side effects and interactions with other medications.
Side Effects and Risks[edit]
The use of MAOIs, including (+)-CPCA, can lead to several side effects. Common side effects include dizziness, headache, and insomnia. More serious risks involve hypertensive crises, especially when combined with certain foods or other medications that increase monoamine levels.
Research and Development[edit]
While (+)-CPCA has shown promise in preclinical studies, further research is needed to fully understand its efficacy and safety profile. Clinical trials are necessary to determine its potential as a therapeutic agent.
(+)-CPCA-CPCA.svg)
