D. Saelens, T. Walle, P. Privitera
1974
Citations
0
Influential Citations
32
Citations
Quality indicators
Journal
The Journal of pharmacology and experimental therapeutics
Abstract
These studies demonstrate the ability of both propranolol and 3-(α-naphthoxy)-1,2-propanediol (propranolol glycol), a major metabolite of propranolol in man, to reduce the lethality of strychnine-induced convulsions in mice. Propranolol glycol appears to be more potent for this effect than propranolol. The onset of action of propranolol glycol is instantaneous but delayed for propranolol. Maximal anticonvulsant activity for propranolol glycol is obtained immediately and for propranolol 10 minutes after administration. Both drugs have a short duration of action, 20 to 25 minutes. The delayed onset of this action of propranolol and the immediate anticonvulsant activity of propranolol glycol strongly suggest that the anticonvulsant properties of propranolol may be related to its conversion to propranolol glycol. Further support for this hypothesis was obtained by the presence of propranolol glycol in the mouse brain during the peak anticonvulsant activity of propranolol. A study of the biotransformation of propranolol glycol demonstrated extensive metabolism which may explain its short duration of action. Propranolol and propranolol glycol have a similar spectrum of gross behavioral effects ranging from quietness at low doses to paralysis at high doses. These observations suggest the possibility that propranolol glycol may be contributing to some of the therapeutically significant effects of propranolol in the central nervous system.