Changes in vascular alpha1-and alpha2-adrenoceptor responsiveness by selegiline treatment

Pharmacoepidemiological studies have reported an excess of mortality with s elegiline, a MAO B inhibitor used in the treatment of Parkinson's disease. The mechanism of this putative adverse effect remains unknown but an intera ction with the sympathetic nervous system was suggested. The aim of the pre sent study was to investigate the influence of selegiline (10 mg/daily, ora lly during one week) on vascular alpha1- and alpha2-adrenoceptor responsive ness in conscious unrestrained dogs. Selegiline significantly increased res ting values of both systolic and diastolic blood pressures and noradrenalin e plasma levels (HPLC without changing heart rate. Moreover, spectral analy sis of systolic blood pressure (Fast Fourier Transformation) showed that se legiline increased the relative energy of a low frequency band without modi fying the total spectrum. ED 50 calculated from dose-pressor response curve s with phenylephrine (after beta-blockade by propranolol), an index of alph a1-adrenoceptor response or with noradrenaline (after alpha1- and beta bloc kade by prazosin plus propranolol), an index of alpha2-adrenoceptor respons e, were significantly higher after selegiline. Selegiline failed to modify the number of platelet alpha2-adrenoceptors measured by [H-3] RX 821002 bin ding. Yohimbine-induced increase in noradrenaline release was significantly more marked after selegiline. These results support the evidence that sele giline induces a vascular alpha1- and alpha2-adrenoceptor-hyposensitivity t hat can be explained by the increase in noradrenaline release elicited by t he drug.