Alprenolol ((RS)-Alprenolol)

Alprenolol is a non-selective β-adrenergic receptor (β-AR) antagonist that is also an antagonist of the serotonin (5-HT) receptor subtypes 5-HT_1A and 5-HT_1B.^1,2 It binds to β₁-, β₂-, and β₃-ARs expressed in CHO cells (K_ds = 15, 0.91, and 117 nM, respectively, for the human receptors) and to 5-HT_1A and 5-HT_1B receptors in rat hippocampal and striatal membranes (K_is = 34 and 134 nM, respectively).^1,2 In vivo, alprenolol (40 mg/kg, i.v.) completely blocks the hyperactivity response of rats to 2-PCPA and L-tryptophan.³ Alprenolol (10 μg, i.v.) inhibits decreases in heart rate and left ventricular systolic pressure induced by the β₂-AR antagonist ICI 118551 in transgenic mice overexpressing the β₂-AR.⁴ It also reduces the level of abnormal prion fibrils (PrP^Sc) in the brain of mice intracerebrally infected with prion disease to less than 20% of control levels when administered in drinking water at a dose of 50 mg/L.⁵

1.Baker, J.G.The selectivity of β-adrenoceptor antagonists at the human β1, β2 and β3 adrenoceptorsBr. J. Pharmacol.144(3)317-322(2005) 2.Langlois, M., Brémont, B., Rousselle, D., et al.Structural analysis by the comparative molecular field analysis method of the affinity of β-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptorsEur. J. Pharmacol.244(1)77-87(1993) 3.Costain, D.W., and Green, A.R.β-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamineBr. J. Pharmacol.64(2)193-200(1978) 4.Bond, R.A., Leff, P., Johnson, T.D., et al.Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the β2-adrenoceptorNature374(6519)272-276(1995) 5.Miyazaki, Y., Ishikawa, T., Kamatari, Y.O., et al.Identification of alprenolol hydrochloride as an anti-prion compound using surface plasmon resonance imagingMol. Neurobiol.(2018)