The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jul 1995
Naloxone-induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil.
Remifentanil is a new mu opioid analgesic of the synthetic phenylpiperidine class. It has an extremely short half-life (10-20 min) due to its breakdown by nonspecific estrases. We studied the effects of continuous infusion of remifentanil, compared with alfentanil, on the respiratory response to hypoxia. ⋯ A significant difference was noted between the two doses of remifentanil. Naloxone administration was associated with reversal of the depressed hypoxic responses during the infusion of alfentanil and the low dose of remifentanil. Termination of remifentanil infusion was associated with a prompt spontaneous recovery of the blunted hypoxic responses that was not detected with alfentanil.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Jul 1995
Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits.
The intravenous general anesthetic 2,6-diisopropylphenol (propofol) potentiates GABAA receptor function, but the precise mechanisms and specificity of this action are still unclear. To study the influence of receptor subunit composition on the action of propofol, 18 different combinations of cloned cDNAs coding for human brain subunit isoforms of the GABAA receptor, as well as mRNAs from mouse brain, were expressed in Xenopus oocytes, and effects of this anesthetic were investigated by the voltage-clamp technique. ⋯ Larger concentrations (10-25 microM) of propofol produced direct activation of Cl- currents, and this action was dependent on the expression of the beta-subunit of the GABAA receptor and did not correlate with the GABA sensitivity of the receptors. These results suggest that propofol exerts a dual effect on GABAA receptors: a positive modulation of the GABA-mediated action on GABAA receptors that is not influenced by the receptor subunit composition, and a specific interaction with the beta-subunit that directly activates the GABAA receptor-coupled Cl- channel.
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J. Pharmacol. Exp. Ther. · Jul 1995
Nitric oxide synthase protects the heart against ischemia-reperfusion injury in rabbits.
The role of nitric oxide (NO) in myocardial ischemia-reperfusion injury is still controversial. To determine the role of NO in the propagation of myocardial injury in a coronary artery occlusion-reperfusion model, we examined the effect of a competitive NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), with and without L-arginine, on the size of the infarct resulting from coronary artery occlusion (30 min) followed by reperfusion (48 hr) in rabbits. L-NAME (300 micrograms/kg, as a bolus, and 100 micrograms/kg/min, i.v.) with and without L-arginine (30 mg/kg, as a bolus, and 10 mg/kg/min, i.v.) was administered immediately before coronary occlusion to 60 min after reperfusion. ⋯ However, the infarct size for the treatment with L-NAME and D-arginine (76.7% +/- 5.7%, n = 6) did not differ from that in the L-NAME-treated rabbits. There was no significant difference in the infarct size between L-arginine-treated (60.1% +/- 7.3%, n = 6) and control rabbits. Rate-pressure products, as an index of myocardial oxygen consumption, were comparable in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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J. Pharmacol. Exp. Ther. · Jun 1995
mu-, delta- and kappa-opiate receptors mediate antinociception in the rat tail flick test following noxious thermal stimulation of one hindpaw.
Experiments were performed to investigate the possible involvement of spinal mu-, delta- and kappa-opiate receptors in mediating the antinociceptive effects of noxious thermal stimulation of one hindpaw on the tail flick reflex in the rat. Male Sprague-Dawley rats were implanted with chronic intrathecal catheters to the lumbar level of the spinal cord. After 5 to 7 days, they were lightly anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). ⋯ In animals pretreated with CSF intrathecally 10 min before the stimulus, an increase in tail flick reaction time was observed peaking at 30 sec after the stimulus. This response was attenuated in a dose-related manner by preadministration of the specific mu-opiate receptor antagonist, beta-funaltrexamine, the specific delta-opiate receptor antagonist, H-Tyr-Tic psi[CH2NH]-Phé-Phe-OH or the specific kappa-opiate receptor antagonist, nor-binaltorphimine. The data show that the antinociceptive effect on the tail withdrawal reflex from a brief noxious thermal stimulus is provoked heterosegmentally by the noxious conditioning stimulus to the hindpaw and is mediated by the endogenous release of ligands that bind to mu-, delta- and kappa-opiate receptors in the spinal cord.
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J. Pharmacol. Exp. Ther. · Jun 1995
Effects of the bradykinin B2 receptor antagonist S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) in different in vivo animal models of inflammation.
The effects of S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (BK)], a new, potent and long-acting BK B2 antagonist, were tested in some in vivo models of inflammation. In rats, S 16118 (0.1 and 1 mg/kg) given i.v. or s.c. delayed the edema formation induced by intraplantar carrageenan injections up to 4 hr after administration, confirming the involvement of kinins in this inflammatory reaction. In guinea pigs treated with atropine, vagal stimulation induced bronchial microvascular leakage. ⋯ In mice, i.p. LPS (25 mg/kg) administration induced over 90% mortality in 96 hr. S 16118 (1 mg/kg x 4), given 30 min before LPS injection and 4, 8 and 24 hr after LPS injection, did not influence the mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)