Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat

Abstract

1 Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2 The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels.3 Sumatriptan at 5 and 50 g,g kg-' had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 tg kg-' of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg', elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose.4 Thus, while a high dose of sumatriptan (500 Stg kg-') exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Effects of Sumatriptan on Cerebral Blood Flow Under Normo- and Hypercapnia in Rats

“…Previous investigators (23–25) reported that sumatriptan did not alter CBF in the steady state. Perren et al (23) have shown that sumatriptan has a highly selective vasoconstrictor action on arteriovenous anastomoses within the cranial circulation of anaesthetized cats, but it does not modify CBF.…”

“…Previous investigators (23–25) reported that sumatriptan did not alter CBF in the steady state. Perren et al.…”

“…Kobari et al. (25), using a cat model, reported that a high dose of sumatriptan (500 µg/kg) exhibited direct vasoconstrictor actions on the cerebral vessels, but low doses in the therapeutic range elicited no vasoconstriction.…”

EP4 prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries

“…Clinically effective treatments such as the 5‐HT 1B/1D receptor agonists, known as triptans, are supposed to derive their antimigraine benefit via inhibition of neuropeptide‐mediated activation of trigeminovascular afferents (Goadsby & Edvinsson, 1993) and vasoconstriction of the cerebral and meningeal vasculature (Humphrey & Feniuk, 1991; Moskowitz, 1993), but not the cerebral microcirculation ( Kobari et al , 1993 ). Of these two interlinked components, electrical or inflammatory mediated stimulation of rat trigeminal ganglia in vitro has been demonstrated to cause a significant release of the neuropeptide calcitonin gene‐related peptide (CGRP) from sensory nerve fibres, and a delayed synthesis and release of PGE 2 from dura mater ( Rich et al , 1996 ; Ebersberger et al , 1999 ).…”

Sumatriptan: aktuelle Erkenntnisse zu Pharmakologie, Wirkungsmechanismus und klinischem Einsatz

“…Messungen des regionalen zerebralen Blutfiusses (rCBF) beim Menschen mittels SPECT (22,57) sowie dopplersonographische Messungen der Blutflufigeschwindigkeit(10,16,17,71) konnten keine oder nur wesentliche Anderungen dieser Parameter nach Gabe von Sumatriptan nachweisen. Auch tierexperimentell wurden, von den oben erwähnten vasokonstriktorischen Effekten abgesehen, keine Anderungen des rCBF oder des Blutvolumens festgestellt(40).Der für die Therapie von Migräne und Clusterkopfschmerz entscheidende Mechanismus scheint damit nicht primär auf der Anderung des zerebralen Blutfiusses bzw.…”