Effects of the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS on alpha-CGRP-induced regional haemodynamic changes in anaesthetised rats.

Several studies suggest that a calcitonin gene-related peptide (CGRP) receptor antagonist may have antimigraine properties, most probably via the inhibition of CGRP-induced cranial vasodilatation. We recently showed that the novel selective CGRP receptor antagonist, BIBN4096BS (1-piperidinecarboxamide, -N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [[R-(R,(R*,S*)]), attenuated the CGRP-induced porcine carotid vasodilatation in a model predictive of antimigraine activity. In order to evaluate the potential safety of BIBN4096BS in migraine therapy, this study was designed to investigate the effects of intravenous BIBN4096BS on alpha-CGRP-induced systemic and regional haemodynamic changes in anaesthetised rats, using radioactive microspheres.

5-HT1B receptors and alpha 2A/2C-adrenoceptors mediate external carotid vasoconstriction to dihydroergotamine.

Dihydroergotamine produces external carotid vasoconstriction in vagosympathectomized dogs by 5-HT(1B/1D) receptors and alpha(2)-adrenoceptors. This study identified the specific subtypes involved in this response. One-minute intracarotid infusions of dihydroergotamine (5.

Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs.

1. Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive trigeminal sensory nerves, seems to be involved in the pathogenesis of migraine. Hence, CGRP receptor antagonists may serve as a novel treatment for migraine.

Effects of BIBN4096BS on cardiac output distribution and on CGRP-induced carotid haemodynamic responses in the pig.

Calcitonin gene related peptide (CGRP) seems to be involved in the pathogenesis of migraine, since plasma CGRP levels increase during the headache phase. In the present study, we investigated the effects of a novel CGRP receptor antagonist, BIBN4096BS (1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl] amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), on the regional cardiac output distribution and on the carotid haemodynamic changes induced by alpha-CGRP in anaesthetised pigs. Treatment with BIBN4096BS (100, 300 and 1000 microg kg(-1), i.

Pharmacological profile of the vascular responses to dopamine in the canine external carotid circulation.

The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.

alpha-Adrenoceptors and Acute Migraine Therapy.

In contrast to the well-established role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT(1B) receptors in mediating constriction within the carotid vascular bed of dogs and pigs, the role of alpha-adrenoceptors and their subtypes has not been as well understood. Using experimental animal models and alpha(1)-adrenoceptor and alpha(2)-adrenoceptor agonists (phenylephrine and BHT-933, respectively) and antagonists (prazosin and rauwolscine, respectively), it was recently shown that activation of either receptor produces a cranioselective vasoconstriction. Subsequently, investigations employing relatively selective antagonists at alpha(1)- (alpha(1A), alpha(1B), alpha(1D)) and alpha(2)- (alpha(2A), alpha(2B), alpha(2C)) adrenoceptor subtypes revealed that specific receptors mediate carotid vasoconstrictor responses.