Current eye research · 2001
Flesinoxan, a 5-HT1A receptor agonist/alpha 1-adrenoceptor antagonist, lowers intraocular pressure in NZW rabbits.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chidlow G, Cupido A, Melena J, Osborne N N
Аннотация
PURPOSE: alpha1-Adrenoceptor antagonists and 5-HT1A receptor agonists reduce intraocular pressure (IOP) in the rabbit. The aims of this study were firstly, to determine the IOP-lowering effects of flesinoxan and selected other hybrid 5-HT1A receptor agonists/alpha1-adrenoceptor antagonists, and secondly, to investigate the mechanism of action of the IOP response to flesinoxan.
METHODS: IOP and total outflow facility were measured in rabbits after administration of hybrid drugs. Inositol phosphates accumulation assays were performed using standard methodologies.
RESULTS: Topical unilateral instillation of the drugs caused dose-related reductions of IOP. Comparison of the compounds tested revealed a potency order of WB 4101 > flesinoxan > 5-methyl-urapidil > or = BMY7378 > urapidil. WB-4101 caused a small increase in total outflow facility whereas flesinoxan had no effect. Measurement of the IC50 values for inhibition of phenylephrine-stimulated inositol phosphates accumulation in rabbit iris-ciliary body revealed a potency order of WB 4101 > 5-methyl-urapidil > flesinoxan > BMY 7378 = urapidil. Topical flesinoxan was ineffective in reversing phenylephrine-induced mydriasis, yet, pretreatment with the 5-HT1A receptor antagonists MDL 73005EF and pindolol only partially blocked the hypotensive effect of topical flesinoxan.
CONCLUSIONS: The present studies indicate the potent and efficacious IOP-lowering capabilities of flesinoxan and certain other ligands with affinity for 5-HT1A receptors/alpha1-adrenoceptors. The exact mechanisms by which these drugs lower IOP in the rabbit are complex but our results indicate that flesinoxan likely reduces aqueous secretion.
METHODS: IOP and total outflow facility were measured in rabbits after administration of hybrid drugs. Inositol phosphates accumulation assays were performed using standard methodologies.
RESULTS: Topical unilateral instillation of the drugs caused dose-related reductions of IOP. Comparison of the compounds tested revealed a potency order of WB 4101 > flesinoxan > 5-methyl-urapidil > or = BMY7378 > urapidil. WB-4101 caused a small increase in total outflow facility whereas flesinoxan had no effect. Measurement of the IC50 values for inhibition of phenylephrine-stimulated inositol phosphates accumulation in rabbit iris-ciliary body revealed a potency order of WB 4101 > 5-methyl-urapidil > flesinoxan > BMY 7378 = urapidil. Topical flesinoxan was ineffective in reversing phenylephrine-induced mydriasis, yet, pretreatment with the 5-HT1A receptor antagonists MDL 73005EF and pindolol only partially blocked the hypotensive effect of topical flesinoxan.
CONCLUSIONS: The present studies indicate the potent and efficacious IOP-lowering capabilities of flesinoxan and certain other ligands with affinity for 5-HT1A receptors/alpha1-adrenoceptors. The exact mechanisms by which these drugs lower IOP in the rabbit are complex but our results indicate that flesinoxan likely reduces aqueous secretion.