Autoradiographic Demonstration of ¹⁴C-Acebutolol Penetration into the Central Nervous System

Abstract

Acebutolol, a relatively weak lipophilic nature in comparison to propranolol, possesses cardioselectivity and membrane-stabilizing properties without intrinsic sympathomimetic action. This betai-selective blocker may affect central nervous activity, judging from the effectiveness for essential tremor and the central nervous system side-effects although the incidence has been low as compared to propranolol. In order to prove this hypothesis, the present study aimed to demonstrate acebutolol penetration into the central nervous system by the use of autoradiography.
Male Sprague-Dawley rats weighing approximately 300 g received 7.5 mg (188.25 μ Ci) of ¹⁴C-acebutolol hydrochloride in 0.5 ml of physiologic saline within 30 seconds from the femoral vein. After 5 minutes the animals were decapitated, and the brains were quickly removed and frozen. Subsequently, the sections 20 μ thick were prepared, which were subjected to autoradiography.
The areas accumulating the highest radioactivity were the ventricles, the cisterns and the tuber cinereum, where the blood brain barrier is lacking. Besides these areas a moderate radioactivity was observed at the mammillary bodies. However, no other parts of the central nervous system revealed a significant location of radioactivity.
From the above results, it was concluded that 14C-acebutolol and possibly its metabolites easily penetrate into cerebrospinal fluid, and the presence of selectively accumulating sites in the central nervous system, if any, has to be pursued in a time-course disposition study.