TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist: characterization of its in vivo bronchodilating action in guinea pigs and cats in comparison with other beta 2-agonists.
Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known beta 2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0 micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen- than spasmogen-induced bronchoconstriction models.
Kikkawa
H
H
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kanno
K
K
Ikezawa
K
K
D000280:Administration, Inhalation; D000284:Administration, Oral; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D006967:Hypersensitivity / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D012129:Respiratory Function Tests; D012701:Serotonin / Q000494:pharmacology
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000662:Amphetamines; D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D006912:Hydroxyquinolines; D015363:Quinolones; D012701:Serotonin; D010047:Ovalbumin; C074413:carmoterol