Leakage of dl-propranolol from cerebrospinal fluid to the bloodstream in the rabbit

Intracerebroventricular (i.c.v.) injection of 500 μg of dl-propranolol in the conscious rabbit resulted in a rise in mean arterial pressure followed by a small but significant fall (3.2 ± 1.4 mm Hg between 2 and 4 hours after injection), as has been observed by others. The same dose injected i.v. resulted in a lowering of mean arterial pressure of 6.0 ± 2.4 mm Hg between 2 and 4 hours injection. After i.c.v. injection there was a rapid rise in plasma propranolol concentration. Ten minutes after i.c.v. injection the concentration of 80% of the level 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 hours. 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 cerebrospinal fluid to plasma it is not possible by means of the technique of i.c.v. injection of the drug to differentiate between central nervous and systemic mechanisms contributing to the lowering of blood pressure.