The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Aug 1992
Randomized Controlled Trial Comparative Study Clinical TrialSubjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability.
The effects of orally administered placebo, diphenhydramine, lorazepam, methocarbamol and placebo were studied in volunteers with histories of recreational substance abuse including sedative/hypnotics. Placebo, diphenhydramine (100, 200 and 400 mg), lorazepam (1 and 4 mg) and methocarbamol (2.25 and 9 g) were tested in a randomized, double-blind crossover study using 14 subjects. Psychomotor and cognitive performance and subject- and observer-rated responses were measured daily before and for 5.5 hr after drug administration. ⋯ The present study clearly differentiated the behavioral and subjective profiles of diphenhydramine, lorazepam and methocarbamol. Consistent with its recognized low abuse liability, diphenhydramine produced fewer increases in measures of positive mood and more adverse effects. The considerable overlap in subjective effect measures of positive mood make further differentiation with respect to abuse liability difficult.
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J. Pharmacol. Exp. Ther. · Aug 1992
Alfaxalone, pentobarbital and diazepam potentiate gamma-aminobutyric acid-induced depolarizations in single myenteric neurons of guinea pig intestine.
Intracellular electrophysiological recordings were made from myenteric neurons of guinea pig ileum maintained in vitro. gamma-Aminobutyric acid (GABA), applied by superfusion (1-300 microM) or by pressure ejection from a fine-tipped pipette positioned near the impaled neuron, depolarized some neurons. GABA-induced depolarizations were mimicked by muscimol (1-100 microM) applied by superfusion and were blocked by bicuculline (30 microM) and picrotoxin (60 microM). The estimated reversal potential for the GABA-induced depolarization was -18 +/- 3 mV when recordings were made with potassium chloride (2 M)-filled microelectrodes. ⋯ Alfaxalone (greater than 1 microM) and pentobarbital (greater than 100 microM) mimicked the GABA-induced depolarization. Cortisol (30-1000 pM) did not alter the amplitude of GABA responses when GABA was applied by pressure ejection (n = 6) or by superfusion (n = 6). These data indicate that GABAA receptors on myenteric neurons contain binding sites for some steroids, barbiturates and benzodiazepines and that responses mediated at enteric GABAA receptors can be modified by drugs acting at these allosteric binding sites.