Nonstereoselective aspects of propranolol pharmacodynamics

Abstract

Twenty years after its discovery, the β-adrenergic blocking agent propranolol continues to interest pharmacologists and clinicians. Its therapeutic profile has extended to areas beyond the purview of the cardiovascular system, and its ocular and central nervous system effects have been well documented. In addition, it still remains a very good pharmacological tool to map out the adrenergic β-receptors in the body, and stereoisomers of propranolol and other β-blockers serve as valuable agents to distinguish between the effects related to β-adrenoceptors and those which are not. The primary purpose of this review is to summarize the evidence indicating that β-adrenergic blocking agents lack stereoselectivity in some of their effects, including several of considerable therapeutic importance. Because many pharmacological actions of propranolol followed a nonsteroselective pattern, the involvement of β-adrenoceptors in them was questioned and this led to the search for alternate mechanisms to explain these effects. Studies with propranolol and some related drugs indicated the involvement of a cholinergic mechanism in their antiarrhythmic, ocular hypotensive and some central effects. Also, a presynaptic inhibitory effect at the skeletal neuromuscular junction has been suggested to explain the benefical effect of propranolol and other β-blockers in tremor. Biochemical studies with these drugs revealed their inhibitory action on the cholinesterase enzyme in blood and other tissues like myocardium and brain. It is thus hypothesized that modulation of cholinergic neurotransmission by propranolol could explain some of its nonstereoselective actions and open new vistas in propranolol pharmacodynamics.