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Titolo:
Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats: pharmacodynamics
Autore:
Wang, Q; Simpao, A; Sun, L; Falk, JL; Lau, CE;
Indirizzi:
Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 chol, Piscataway, NJ 08854 USA
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 3, volume: 153, anno: 2001,
pagine: 341 - 352
Fonte:
ISI
Lingua:
ENG
Soggetto:
TIMING PERFORMANCE DEFICITS; RELATING DRL PERFORMANCE; LOCOMOTOR-ACTIVITY; SQUIRREL-MONKEYS; PHARMACOKINETICS; ALPRAZOLAM; CAFFEINE; INTRAPERITONEAL; DERIVATIVES; MIDAZOLAM;
Keywords:
cocaine; norcocaine; pharmacodynamic; pharmacokinetic; routes of administration;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Lau, CE Rutgers State Univ, Dept Psychol, 152 Frelinghuysen Rd, Piscataway, NJ 08854 USA Rutgers State Univ 152 Frelinghuysen Rd Piscataway NJ USA 08854 SA
Citazione:
Q. Wang et al., "Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats: pharmacodynamics", PSYCHOPHAR, 153(3), 2001, pp. 341-352

Abstract

Rationale: Oral cocaine is more effective than IV cocaine by pharmacokinetic and pharmacodynamic analysis. One explanation is involvement of the active metabolite, norcocaine, in cocaine's effects. Objectives: To evaluate norcocaine's contribution to oral cocaine's effects, norcocaine's effects as a parent compound were determined and compared to those of cocaine using a differential reinforcement of low rate (DRL 45-s) schedule and spontaneous activity (large and small movements) after IV and PO routes of administration. Methods: The effects of cocaine and norcocaine on DRL performance (shorter-response and reinforcement rates) and spontaneous activity were investigated in 3-h sessions. The changes in effects across time (effect-time profiles) and dose-response curves (DRCs) were constructed to evaluate the duration of action and potency (ED50) of both drugs. Results: Under the DRL 45-s schedule, effect-time profiles showed both drugs via the two routes of administration significantly increasing and decreasing shorter-response ratesand reinforcement rates, respectively. However, cocaine produced greater effects on shorter-response rates than norcocaine, while both drugs producedcomparable effects on reinforcement rates. For spontaneous activity, although IV cocaine, PO cocaine, and PO norcocaine dose- and time-dependently increased spontaneous activity, cocaine's effects were more profound than those of norcocaine. Effect-time profiles revealed that the duration of drug action was a function of dose, route, and behavioral paradigm used. According to ED50 values, IV cocaine was more effective than PO cocaine; however, PO cocaine was more effective than IV cocaine as judged by ED50 values corrected for absolute oral bioavailability. Conclusions: Norcocaine's contribution to oral cocaine's effects on DRL performance is evident. Other mechanism(s), such as a greater acute tolerance to IV cocaine's effects than to PO cocaine's effects, can be excluded.

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Documento generato il 02/06/20 alle ore 21:45:35