INTRINSIC SYMPATHOMIMETIC ACTIVITY OF BETA-ADRENOCEPTOR BLOCKING-DRUGS AT CARDIAC AND VASCULAR BETA-ADRENOCEPTORS

In the anaesthetised, reserpinised rat isoprenaline causes tachycardia and depressor responses: these effects are due to stimulation of β1 (cardiac) and β2 (vascular) adrenoceptors. Salbutamol also produces tachycardia and depressor responses. (±) and (-) bufuralol, and its carbinol and ketone metabolites, produce similar responses indicating intrinsic sympathomimetic activity (ISA) at β1 and β2 adrenoceptors; (+) bufuralol lacks ISA. Pindolol and oxprenolol also cause tachycardia and a depressor effect; oxprenolol is weakly active in producing the latter response. Propranolol is devoid of ISA; 4-hydroxypropranolol causes tachycardia with a negligible fall in blood pressure. Practolol causes only tachycardia. These results demonstrate that the reserpinised rat is a suitable experimental model for the demonstration of ISA at β1 and β2 adrenoceptors. Non-selective β-adrenoceptor blocking drugs produce stimulation at β2 (vascular) adrenoceptors as well as β1 (cardiac) adrenoceptors. © 1978.