β‐ADRENOCEPTOR ANTAGONISTS: STUDIES ON BEHAVIOUR (DELAYED DIFFERENTIATION) IN THE MONKEY (Macaca mulatta)

Abstract

IActivity of six ,B-adrenoceptor antagonists was studied on behavioural activity (delayed differentiation) in the monkey (Macaca mulatta). The drugs, three relatively lipophilic antagonists (propranolol, oxprenolol and metoprolol), and three relatively hydrophilic antagonists (acebutolol, atenolol and sotalol), were given by intraperitoneal injection (5 to 30 mg/kg). 2 With atenolol (25 to 30 mg/kg), total response time was increased, but there was no effect on the number of correct responses. With acebutolol (25 to 30 mg/kg), the number of correct responses was reduced, but there was no effect on total response time. With metoprolol (25 to 30 mg/kg), there was an increase in total response time and a decrease in the number of correct responses, and correct responses were decreased 4 h after injection over the whole dose range (5 to 30 mg/kg). 3 Some animals failed to respond or complete the task with 30 mg/kg oxprenolol, 25 mg/kg sotalol and 20 mg/kg propranolol. With 25 mg/kg oxprenolol, the total response time was increased and the number of correct responses was decreased. With 5-20 mg/kg sotalol, total response time was increased, but there was no effect on the number of correct responses. With 15 mg/kg of (±)propranolol and its isomers, there were increases in total response time and decreases in correct responses. 4 The studies suggest that lipophilic antagonists, such as propranolol, oxprenolol and metoprolol, are likely to have, at least, effects on the central nervous system, while hydrophilic antagonists may modify the peripheral nervous system. In the dose-ranges studied, propranolol had the greatest, and atenolol and acebutolol had the least effects. Atenolol and acebutolol may prove to be particularly useful in man when disturbances of the nervous system are to be avoided.

Importance of Membrane Stabilizing Effect in Massive Overdose of Propranolol: Plasma Level Study in a Fatal Case

“…Nicholson & Wright (1980) suggested that membrane stabilisation may be a basis for the central effects of propranolol. It was worth noting that the most frequently observed side effects of propranolol were drowsiness, ataxia and hypotension, not bradycardia or congestive heart failure, in psychiatric patients who took large doses of propranolol (up to 600 mg QDS) for the control of schizophrenic symptoms (Sheppard, 1979).…”

Central effects of beta‐adrenoceptor antagonists. II‐ Electroencephalogram and body sway.

“…Drugs which impair performance, such as oxazepam and diazepam, modify body sway, whereas similar drugs without obvious behavioural effects, such as clobazam, dipotassium chlorazepate and desmethyldiazepam tend to leave body sway unaffected (Baron et al, 1977;Sittig et al, 1982;Patat & Foulhoux, 1985). However, the effect of atenolol could have been mediated through the peripheral control of posture, since impaired psychomotor performance is not an obvious effect of this drug (Nicholson & Wright, 1980;Currie et al, 1988).…”