Cardiovascular safety profile of almotriptan, a new indolic derivative for the treatment of migraine.
Almotriptan is a new 5-HT(1B/1D) receptor agonist effective for treating acute migraine attacks with or without aura. As 3-5% of patients treated with sumatriptan experience chest symptoms thought to be of cardiac origin, we investigated the cardiovascular safety profile of almotriptan in comparison with that of sumatriptan in six animal models. Almotriptan did not modify blood pressure or heart rate in conscious telemetered normotensive Wistar rats (p.o.), in anaesthetised beagle dogs (i.v.), or in conscious beagle dogs (i.v.), and only produced transient increases when administered (s.c.) to telemetered cynomolgus monkeys. Almotriptan did not consistently affect the duration of the electrocardiogram (ECG) intervals in anaesthetised beagle dogs even when the drug was administered into the coronary artery, nor was ECG morphology altered in telemetered cynomolgus monkeys. In contrast, sumatriptan i.v. consistently increased mean blood pressure and heart rate in conscious beagle dogs. Finally, almotriptan did not modify coronary blood flow at a dose of up to 0.3 mg/kg i.v. in conscious beagle dogs. Thus, almotriptan has a favourable cardiovascular safety profile.
Gras
J
J
Pharmacological Development Department, Almirall Prodesfarma, Research Center, Cardener 68-74, 08024-, Barcelona, Spain. jgras@almirallprodesfarma.com
Cardelús
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I
Llenas
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Palacios
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JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000378:metabolism; D012449:Safety; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D014363:Tryptamines
D007211:Indoles; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan; D018170:Sumatriptan