[Pharmacological properties of (+/-)-4-[2-hydroxy-3-(3-(2-methoxyphenoxy)-2-propylamino)propoxy]-1(2H) -isoquinolinone (N-1518), a new combined alpha- and beta-adrenoceptor blocking drug]
| Autor: | Toshiji Sugai |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Agonist
Male medicine.drug_class Vasodilator Agents Adrenergic beta-Antagonists Guinea Pigs Alpha (ethology) Vasodilation Blood Pressure Hindlimb Pharmacology In Vitro Techniques Phenoxypropanolamines Dogs Oral administration Heart Rate Rats Inbred SHR medicine Animals Labetalol Anesthetics Local Adrenergic alpha-Antagonists Chemistry Local anesthetic Rats Inbred Strains Stereoisomerism Isoquinolines Rats Femoral Artery Blood pressure Regional Blood Flow Female medicine.drug |
| Zdroj: | Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 96(3) |
| ISSN: | 0015-5691 |
| Popis: | The alpha, beta-adrenergic blocking, antihypertensive and vasodilating properties of N-1518 were compared with those of labetalol. N-1518 blocked alpha- and beta-adrenoceptors competitively as indicated by parallel rightward displacement of the dose-response curve of each agonist in isolated organs and in anesthetized dogs. As judged by pA2 values and DR10 values, N-1518 was as potent as labetalol in blocking alpha- and beta-adrenoceptors. The beta 1/alpha 1 ratio of N-1518 was 8.3 for pA2 values in isolated organs and 13.6 for DR10 values in anesthetized dogs, respectively. N-1518 inhibited dose-dependently the pressor response to intravenous administration of noradrenaline, but labetalol did not depress the response to noradrenaline in anesthetized dogs. N-1518 is composed of four optical isomers. The SR-isomer was the most potent in blocking beta-receptors, and the RR-isomer was the most potent in blocking alpha-receptors. N-1518 has no intrinsic sympathomimetic activity in reserpinized rats and has no local anesthetic activity in guinea pigs. Single oral administration of N-1518 produced a fall in blood pressure in conscious SHR and renal hypertensive dogs without causing tachycardia. Intra-arterially administered N-1518 in the dog hindlimb resulted in vasodilation as indicated by the increase in blood flow. The magnitude of the responses was approximately 3 times more potent than that of labetalol. |
| Databáze: | OpenAIRE |
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