Rats were rendered tolerant to ethanol or pentobarbital by daily oral administration. Motor impairments after test doses of ethanol or pentobarbital were measured prior to and at various times during chronic treatment in order to assess the degree of tolerance development. Chronic administration of p-chlorophenylalanine (p-CPA) in a dosage regimen which produced and maintained approximately 95% depletion of brain serotonin (5-HT) did not alter motor impairment after initial acute administration of ethanol or pentobarbital. However, the rate of tolerance development to the motor-impairing effects of both drugs was slowed down in p-CPA-treated rats, p-CPA did not appear to exert this effect by altering the disposition of ethanol or pentobarbital, since blood levels determined 20 min after administration of the test doses were similar in animals treated with p-CPA and in controls. These findings suggest that brain 5-HT may have a role in tolerance development to ethanol and pentobarbital.

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The use of local anesthesia with intravenous sedation for inguinal hernia repair in the adolescent age group seems feasible and requires further prospective study.

The antihypertensive effects of a 20 mg tablet of nifedipine were compared with those of hydralazine in a randomized, double-blind, placebo-controlled study. Nineteen patients with a diastolic blood pressure (BP) between 95 and 120 mm Hg despite combined diuretic and beta-blocker therapy completed the protocol. After 2 weeks of placebo each subject received increasing doses of nifedipine (20, 40, and 60 mg b.i.d.) and hydralazine (25, 50, and 100 mg b.i.d.) if tolerated or until goal BP (supine and standing diastolic BP less than 85 mm Hg) was achieved. Both nifedipine and hydralazine significantly lowered supine BP from placebo baseline (146 +/- 3/96 +/- 2 mm Hg) to 119 +/- 3/80 +/- 2 and 129 +/- 2/81 +/- 2 mm Hg, respectively. The decrease in systolic BP with nifedipine was significantly lower than that with hydralazine at 9 weeks. Neither drug significantly altered heart rate. Mean left ventricular ejection fractions were similar for nifedipine (67% +/- 2%), hydralazine (69% +/- 3%), and placebo (66% +/- 2%). The nifedipine tablet appears to be an effective antihypertensive agent in patients whose BP remains high despite combined diuretic and beta-blocker therapy.