K. Messlinger et al., EFFECTS OF THE 5-HT1 RECEPTOR AGONISTS, SUMATRIPTAN AND CP-93,129, ONDURAL ARTERIAL FLOW IN THE RAT, European journal of pharmacology, 332(2), 1997, pp. 173-181
The blood flow in and around the medial meningeal artery (dural arteri
al flow) was recorded in the exposed parietal dura mater encephali of
the anesthetized rat using laser Doppler flowmetry. Local electrical s
timulation of the dura mater (pulses of 0.5 ms delivered at 7.5-17.5 V
and 5 or 10 Hz for 30 a) caused temporary increases in dural arterial
flow. The effects of the 5-HT1 receptor agonists sumatriptan and CP 9
3,129 on the basal flow and the electrically evoked increases in flow
were examined. Topical administration of undiluted sumatriptan (12 mg/
ml) lowered the basal and the evoked flow by 20% on average. Systemic
(i.v.) administration of sumatriptan (0.24, 0.72 and 3.6 mu mol/kg) ca
used a short-lasting reduction of the evoked flow increases only at th
e higher doses while the basal flow was not significantly altered. Sys
temic administration of CP 93,129 (0.46 and 4.6 mu mol/kg) caused no s
ignificant changes of the basal and the evoked flow. At a dose of 23 m
u mol/kg CP 93,129 lowered the basal flow by 20% and the evoked flow b
y 30% for 20 min. The systemic arterial pressure was not significantly
attend by sumatriptan and CP 93,129 within the whole range of doses.
It is suggested that sumatriptan and CP 93,129 at high doses exert inh
ibitory effects on those fine afferent nerve fibers which release the
calcitonin gene-related peptide, since this neuropeptide mediates the
evoked increases in dural arterial flow. (C) 1997 Elsevier Science B.V
.