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Titolo:
Antagonism of the discriminative stimulus effects of positive gamma-aminobutyric acid(A) modulators in rhesus monkeys discriminating midazolam
Autore:
Lelas, S; Gerak, LR; France, CP;
Indirizzi:
Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA USA Louisiana State Univ New Orleans LA USA t Pharmacol, New Orleans, LA USA Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA USA Louisiana State Univ New Orleans LA USA Excellence, New Orleans, LA USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 294, anno: 2000,
pagine: 902 - 908
SICI:
0022-3565(200009)294:3<902:AOTDSE>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE RECEPTOR ANTAGONIST; APPARENT PA(2); RO 15-1788; DIAZEPAM; RATS; FLUMAZENIL; ZOLPIDEM; AGONISTS; LIGANDS; DRUGS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: France, CP Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio,TX 78229 USA Univ Texas 7703 Floyd Curl Dr San Antonio TX USA 78229 8229 USA
Citazione:
S. Lelas et al., "Antagonism of the discriminative stimulus effects of positive gamma-aminobutyric acid(A) modulators in rhesus monkeys discriminating midazolam", J PHARM EXP, 294(3), 2000, pp. 902-908

Abstract

The extent to which individual subtypes of benzodiazepine receptors are functionally independent has not been elucidated in vivo. This study used apparent pA(2) analysis to test the hypothesis that a single receptor subtype mediates the discriminative stimulus effects of midazolam, triazolam, and diazepam, three positive gamma-aminobutyric acid(A) (GABA(A)) modulators. Four rhesus monkeys discriminated 0.56 mg/kg midazolam from vehicle under a fixed-ratio 5 schedule of stimulus-shock termination. Midazolam, triazolam, and diazepam increased responding on the midazolam-appropriate lever. The neutral GABA(A) modulator flumazenil shifted dose-effect curves for triazolam and diazepam to the right, and the negative GABA(A) modulators Ro 15-4513and ethyl beta-carboline-3-carboxylate (beta-CCE) shifted dose-effect curves for midazolam and triazolam to the right. Slopes of Schild plots for flumazenil and Ro 15-4513 conformed to unity. The apparent pA(2) values were 7.41 and 7.69 for flumazenil in combination with triazolam and diazepam, respectively, and 7.53 and 6.88 for Ro 15-4513 in combination with midazolam and triazolam, respectively. The slope of the Schild plot for beta-CCE in combination with midazolam deviated from unity, Slopes of Schild plots obtained with flumazenil and Ro 15-4513 support the notion that a single benzodiazepine receptor subtype mediates the effects of midazolam, triazolam, or diazepam. The similarity in apparent pA(2) values for flumazenil in combination with triazolam and diazepam or for Ro 15-4513 in combination with midazolam and triazolam suggests that the same subtype mediates the effects of these positive modulators. In contrast, beta-CCE and midazolam do not appear to interact in a simple, competitive manner.

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Documento generato il 09/04/20 alle ore 00:11:23