SUMATRIPTAN INHIBITS THE RELEASE OF CGRP AND SUBSTANCE-P FROM THE RATSPINAL-CORD

THE possible presynaptic action of the anti-migraine drug sumatriptan on primary afferent fibres containing substance P and/or calcitonin ge ne-related peptide was investigated on superfused rat horizontal spina l cord slices with attached dorsal roots. Electrical stimulation of do rsal roots triggered a significant overflow of both peptides; this cou ld be reduced by sumatriptan in a concentration-dependent manner. As e xpected from the involvement of 5-HT1B/(1D beta) receptors, methiothep in, (-)tertatolol and GR 127,935, but not WAY 100,635, prevented the i nhibitory effect of sumatriptan. These data support the idea that the anti-migraine action of sumatriptan may involve, at least in part, a p resynaptic inhibitory control of nociceptive (trigeminovascular) subst ance P- and/or calcitonin gene-related peptide-containing sensory fibr es.