Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine
| Autor: | José Palacios, Josep Bou, Teresa Doménech, Ascensión Heredia, Jaume Puig, Dolors Fernández-Forner, Jordi Gras, Jorge Beleta |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Agonist medicine.medical_specialty Indoles Swine medicine.drug_class Migraine Disorders Transfection Muscle Smooth Vascular Dogs Almotriptan Internal medicine Cyclic AMP medicine Animals Humans Vasoconstrictor Agents Saphenous Vein Rats Wistar Receptor Mesenteric arteries 5-HT receptor Pharmacology Dose-Response Relationship Drug Sumatriptan business.industry Colforsin Meningeal Arteries Tryptamines Rats Serotonin Receptor Agonists medicine.anatomical_structure Endocrinology Mechanism of action Vasoconstriction Cattle Rabbits Serotonin medicine.symptom business HeLa Cells medicine.drug |
| Zdroj: | European Journal of Pharmacology. 410:33-41 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(00)00876-1 |
| Popis: | Almotriptan (3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl )-1H-indo le) has been studied in several models predictive of activity and selectivity at 5-HT receptors. Almotriptan showed low nanomolar affinity for the 5-HT(1B) and 5-HT(1D) receptors in several species, including the human, while affinity for 5-HT receptors other than 5-HT(1B/1D) was clearly less. Affinity for 5-HT(7) and 5-HT(1A) receptors was approximately 40 and 60 times lower than that for 5-HT(1B/1D) receptors, respectively. Almotriptan did not exhibit significant affinity for several non-5-HT receptors studied up to 100 microM. Almotriptan inhibited forskolin-stimulated cyclic AMP accumulation in HeLa cells transfected with 5-HT(1B) or 5-HT(1D) human receptors. In this model, almotriptan had the same efficacy as serotonin and an affinity in the low nanomolar range. It induced vasoconstriction in several vessels in which it was compared with sumatriptan. In isolated dog saphenous veins, almotriptan elicited concentration-dependent contractions with an EC(50) of 394 nM. In both these systems, almotriptan behaved as a full agonist. Infusion of almotriptan into the porcine meningeal vasculature induced vasoconstriction. In contrast, in the pig renal and rabbit mesenteric arteries, it had a very low maximal efficacy even at 100 microM, with similar results obtained in the rabbit renal artery. The results suggest that almotriptan is a potent and selective 5-HT(1B/1D) receptor agonist, with selectivity for the cranial vasculature as compared with peripheral vessels. |
| Databáze: | OpenAIRE |
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