The effects of perhexiline on the sympathetic nervous system.

The effects of perhexiline on sympathetic nervous system function were studied in vitro and in vivo. Perhexiline decreased the field stimulation-induced contractile response of the isolated vas deferens and significantly decreased the quantity of norepinephrine released during stimulation of this preparation. In vivo studies in dogs showed that perhexiline reduced the heart rate response to cardiac accelerator nerve stimulation, an effect not associated with an increase in cholinergic tone or beta adrenergic blockade. Measurements of norepinephrine released from the heart during cardiac nerve stimulation showed that perhexiline (3 mg/kg) decreased norepinephrine release by approximately 35%. These results suggest that a presynatpic effect of perhexiline, which results in a decrease in norepinephrine release, contributes significantly to the attenuated heart rate response which occurs after administration of this drug. A decrease in transmitter release during sympathetic stimulation could play an important role in the mechanism for the protective effects of perhexiline in myocardial ischemic damage.