Functional profile of almotriptan in animal models predictive of antimigraine activity.
Almotriptan is a new 5-HT(1B/1D) receptor agonist whose clinical efficacy for the treatment of migraine attacks has been demonstrated in Phase III clinical trials. We now compare the functional profile of almotriptan (assessed using animal models) with that of sumatriptan. Almotriptan selectively increased carotid vascular resistance in anaesthetised cats after intravenous or intraduodenal administration (ED(100)=11 microg/kg, i.v.; ED(50)=339 microg/kg, i. d.) and in anaesthetised beagle dogs following intravenous administration (ED(50)=116 microg/kg). A study in anaesthetised cats also demonstrated that almotriptan acts by selectively increasing the resistance of the carotid arteriovenous anastomoses without adversely affecting brain irrigation. In addition, almotriptan inhibited meningeal extravasation produced by electrical stimulation of the trigeminal ganglion in anaesthetised guinea pigs in the dose range of 0.3-3 mg/kg, i.v. In conclusion, almotriptan is both a selective constrictor affecting intracranial blood vessels and an inhibitor of neurogenically evoked plasma protein extravasation of the dura mater.
Gras
J
J
Pharmacological Development Department, Almirall Prodesfarma, Research Center, Cardener 68-74, 08024-, Barcelona, Spain. jgras@almirallprodesfarma.com
Bou
J
J
Llenas
J
J
Fernández
A G
AG
Palacios
J M
JM
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D002415:Cats; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects; D008881:Migraine Disorders / Q000188:drug therapy*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D012039:Regional Blood Flow; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D014363:Tryptamines; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D007211:Indoles; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan; D018170:Sumatriptan