Source:http://linkedlifedata.com/resource/pubmed/id/12649362
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
|
pubmed:dateCreated |
2003-3-21
|
pubmed:abstractText |
The present study investigated the pharmacological properties of a piperidine-based novel cocaine analog, namely, (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylic acid [(+)-CPCA]. Like cocaine, (+)-CPCA inhibited rat synaptosomal dopamine and norepinephrine uptake with high affinity, but was 33-fold less potent than cocaine in inhibiting serotonin uptake. Like cocaine, (+)-CPCA is a locomotor stimulant, although it was less potent and efficacious than cocaine. Importantly, pretreatment with (+)-CPCA dose dependently blocked the locomotor stimulant effects of cocaine in rats. (+)-CPCA completely substituted for cocaine in drug discrimination tests, although it was about 3 times less potent than cocaine. It was also self-administered by rats. Unexpectedly, (+)-CPCA did not enhance cocaine-induced convulsions in mice. As expected from rodent studies, rhesus monkeys readily self-administered (+)-CPCA. However, compared with cocaine, (+)-CPCA showed limited reinforcing properties in rats as assessed by both fixed and progressive ratio intravenous drug self-administration tests. These results collectively suggest that (+)-CPCA has an atypical pharmacological profile having both cocaine-like "agonist" and some cocaine "antagonist" properties. These properties of (+)-CPCA suggest that it may have utility in the treatment of cocaine craving and dependence.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0022-3565
|
pubmed:author |
pubmed-author:AraldiGian LucaGL,
pubmed-author:BalsterRobert LRL,
pubmed-author:BandyopadhyayBidhan CBC,
pubmed-author:BeardsleyPatrick MPM,
pubmed-author:CarmonaGilbertoG,
pubmed-author:DeschauxOlivierO,
pubmed-author:JohnsonKenneth MKM,
pubmed-author:KozikowskiAlan PAP,
pubmed-author:MunzarPatrikP,
pubmed-author:SmithMiles PMP,
pubmed-author:TellaSrihari RSR
|
pubmed:issnType |
Print
|
pubmed:volume |
305
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
143-50
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:12649362-Animals,
pubmed-meshheading:12649362-Cocaine,
pubmed-meshheading:12649362-Discrimination Learning,
pubmed-meshheading:12649362-Humans,
pubmed-meshheading:12649362-Infusions, Intravenous,
pubmed-meshheading:12649362-Macaca mulatta,
pubmed-meshheading:12649362-Mice,
pubmed-meshheading:12649362-Motor Activity,
pubmed-meshheading:12649362-Piperidines,
pubmed-meshheading:12649362-Rats,
pubmed-meshheading:12649362-Rats, Sprague-Dawley,
pubmed-meshheading:12649362-Self Administration
|
pubmed:year |
2003
|
pubmed:articleTitle |
Mixed cocaine agonist/antagonist properties of (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate, a piperidine-based analog of cocaine.
|
pubmed:affiliation |
Drug Discovery Program, Departments of Neurology, Georgetown University Medical Center, Washington, DC, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|