Effect of Propranolol, Alprenolol, Pindolol, and Bopindolol on β2-Adrenoceptor Density in Human Lymphocytes

Abstract

Abrupt withdrawal of beta-adrenoceptor antagonists may lead to "rebound effects." To investigate the position of the new nonselective beta-adrenoceptor antagonist bopindolol [with moderate intrinsic sympathomimetic activity (ISA)], this drug was compared with propranolol (no ISA), alprenolol (weak ISA), and pindolol (marked ISA). The effects on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]iodocyanopindolol (ICYP) binding--were investigated in healthy volunteers aged 23-35 years. None of the test drugs changed the affinity of ICYP for beta 2 adrenoceptors. Propranolol treatment (4 X 40 mg/day) increased the density of beta 2-adrenoceptors by 25% after 2 days; during treatment beta 2-adrenoceptor density remained elevated. After withdrawal of propranolol, beta 2-adrenoceptor density declined slowly, being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h, though heart rate was significantly increased. Alprenolol treatment (4 X 100 mg/day) did not significantly affect beta 2-adrenoceptor density. Pindolol treatment (2 X 5 mg/day) caused a 50% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. Bopindolol treatment (2 mg/day) caused a 40% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. It is concluded that the ISA may play an important role in modulating beta 2-adrenoceptor density and hence tissue responsiveness to beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)