LEAKAGE OF DL-PROPRANOLOL FROM CEREBROSPINAL-FLUID TO BLOOD-STREAM IN RABBIT

Abstract

Intracerebroventricular (i.c.v.) injection of 500 .mu.g of dl-propranolol in the conscious rabbit resulted in a rise in mean arterial presure followed by a small but significant fall (3.2 .+-. 1.4 mm Hg between 2-4 h after injection). The same dose injected i.v. resulted in a lowering of mean arterial pressure of 6.0 .+-. 2.4 mm Hg between 2-4 h after injection. After i.c.v. injection there was a rapid rise in plasma propranolol concentration. Ten min after i.c.v. injection the 80% concentration level was reached after giving the same dose i.v. After i.c.v. injection there was significant blockade of cardiac .beta.-adrenoreceptors for at least 2 h. This blockade was determined from the degree of attenuation of isoproterenol-induced tachycardia in rabbits subjected to presynaptic sympathetic nerve block with guanethidine and to vagal block with methscopolamine. Because of the rapid leakage of propranolol from CSF to plasma it is not possible by means of i.c.v. drug injection to differentiate between CNS systemic mechanisms contributing to the lowering of blood pressure.