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Titolo:
Locomotor stimulant effects of novel phenyltropanes in the mouse
Autore:
Kimmel, HL; Carroll, FI; Kuhar, MJ;
Indirizzi:
Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA Emory Univ Atlanta GA USA 30329 eg Primate Res Ctr, Atlanta, GA 30329 USA Res Triangle Inst, Res Triangle Pk, NC 27709 USA Res Triangle Inst Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Titolo Testata:
DRUG AND ALCOHOL DEPENDENCE
fascicolo: 1, volume: 65, anno: 2001,
pagine: 25 - 36
SICI:
0376-8716(200112)65:1<25:LSEONP>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
2-SUBSTITUTED COCAINE ANALOGS; DOPAMINE-TRANSPORTER; LIGAND-BINDING; HIGH-AFFINITY; MONOAMINE TRANSPORTERS; RECEPTOR ANTAGONISTS; RECOGNITION SITES; SQUIRREL-MONKEY; REUPTAKE SITES; PRIMATE BRAIN;
Keywords:
cocaine; locomotor activity; mouse; phenyltropane analogs; pharmacotherapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Kimmel, HL Emory Univ, Yerkes Reg Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA Emory Univ 954 Gatewood Rd NE Atlanta GA USA 30329 GA 30329 USA
Citazione:
H.L. Kimmel et al., "Locomotor stimulant effects of novel phenyltropanes in the mouse", DRUG AL DEP, 65(1), 2001, pp. 25-36

Abstract

With the hypothesis that 3-phenyltropane analogs of cocaine might be useful as cocaine medications, 17 analogs (RTI-51, RTI-55, RTI-108, RTI-112, RTI-113, RTI-116, RTI-120, RTI-121, RTI-126, RTI-139, RTI-141, RTI-150, RTI-171, RTI-177, RTI-199, RTI-204, and RTI-219) were characterized for their potency and selectivity at the monoamine transporters in a previous study. Based on their affinities to the transporters in this earlier study, the analogs were classified as nonselective (cocaine, RTI-51, RTI-55, RTI-108, RTI-112. RTI-116, RTI-126, and RTI-139) or dopamine transporter (DAT) selective (RTI-113, RTI-120, RTI-121, RTI-141, RTI-150, RTI-171, RTI-177, RTI-199, RTI-204, and RTI-219). In the present study, the locomotor stimulating effects of these analogs were compared to those of cocaine to obtain a measure ofin vivo activity. Each analog was more potent than cocaine in the in vivo assay, as observed in the earlier in vitro studies. Most of these compoundswere as efficacious as cocaine, but RTI-51. RTI-108, RTI-113, RTI-121, RTI-139, RTI-141, RTI-177, RTI-204, and RTI-219 were longer acting. Although no correlation between chemical structure and transporter selectivity was found, the short-acting DAT-selective analogs, RTI-120, RTI-150, RTI-171, andRT1-199, all contained a methyl group in the X position of the WIN 35,065-2 molecule. The positive correlation of the IC(50)s for the DAT to potencies for increasing locomotor activity suggested that binding to DAT was responsible for some, if not most, of the locomotor effects of these compounds. Several compounds, including RTI-113 and RTI-177, exhibited properties ideal for medications for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 21:03:19