Effect of some acute and prophylactic antimigraine drugs on the vasodepressor sensory CGRPergic outflow in pithed rats.

AIMS: This study analyzed in pithed rats the effect of several acute and prophylactic antimigraine drugs on the CGRPergic vasodepressor sensory outflow, in an attempt to investigate systemic cardiovascular effects in a model unrelated to migraine.

MAIN METHODS: Male Wistar pithed rats were pretreated with continuous i.v. infusions of hexamethonium (2 microg/kg.min; to block autonomic outflow) and methoxamine (15-20 microg/kg.min; to maintain diastolic blood pressure at around 130 mmHg). Under these conditions, the effect of both electrical stimulation (0.56-5.6 Hz; 50 V and 2 ms) of the spinal cord (T(9)-T(12)) or i.v. bolus injections of exogenous alpha-CGRP (0.1-1 microg/kg) were studied in animals pretreated with continuous i.v. infusions of sumatriptan (1-100 microg/kg.min), ergotamine (0.18-0.56 microg/kg.min), dihydroergotamine (1-10 microg/kg.min), magnesium valproate (1000-1800 microg/kg.min), propranolol (100-300 microg/kg.min) or their respective vehicles.

KEY FINDINGS: Electrical stimulation of the spinal cord and i.v. bolus injections of exogenous alpha-CGRP resulted in, respectively, frequency- and dose-dependent decreases in diastolic blood pressure without affecting heart rate. Moreover, the infusions of sumatriptan, ergotamine and dihydroergotamine, but not of magnesium valproate, propranolol or their respective vehicles, dose-dependently inhibited the vasodepressor responses to electrical stimulation. In contrast, sumatriptan (10 microg/kg.min), ergotamine (0.31 microg/kg.min) and dihydroergotamine (3 microg/kg.min) failed to inhibit the vasodepressor responses to exogenous alpha-CGRP.

SIGNIFICANCE: The above findings suggest that the acute (rather than the prophylactic) antimigraine drugs attenuate the vasodepressor sensory outflow mainly by prejunctional mechanisms. This may be of particular relevance when considering potential cardiovascular adverse effects by acute antimigraine drugs.