[Pharmacological action of SN-408, a novel long-acting selective beta 2-adrenoceptor agonist].
The bronchodilating effect and other related pharmacological properties of SN-408 were studied in comparison with those of isoproterenol, salbutamol and procaterol. SN-408 caused concentration-dependent relaxation of isolated guinea pig trachea via the beta 2-adrenoceptor. The order of relaxation potency was: procaterol greater than SN-408 greater than or equal to isoproterenol greater than salbutamol, but the duration of the action of SN-408 was far longer than those of other beta-agonists. Positive chronotropic and inotropic actions of SN-408 in isolated guinea pig right atria and left atria were less potent than those of other beta-agonists. In isolated guinea pig lung tissues, SN-408 increased cyclic AMP contents. Also in vivo, SN-408 showed dose-dependent bronchodilating action by i.v. administration in anesthetized guinea pigs and by inhalation in conscious guinea pigs. Bronchodilating actions of SN-408 were less potent than those of procaterol and isoproterenol, but the duration of action of SN-408 was far longer than those of other beta-agonists. SN-408 showed no evidence of the development of tolerance to the bronchodilating action. SN-408 caused small tachycardia in guinea pigs by i.v. and inhalation. SN-408 given i.v. suppressed vascular permeability in mice. These results indicate that SN-408 is a long-acting and selective beta 2-stimulant bronchodilator.
Nishimura
M
M
Tokyo Research Laboratories, Nippon Glaxo Ltd., Japan.
Okiyama
M
M
Fujiwara
H
H
Kudo
M
M
Simizu
M
M
Maeda
M
M
Yamada
M
M
Toshimitsu
Y
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D017265:Procaterol; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D007545:Isoproterenol; D000420:Albuterol; D017265:Procaterol