Pharmacodynamics of a new selective beta2-adrenergic bronchodilator 3-(4-methoxybenzylamino)-4-hydroxy-alpha-(tert. butylaminomethyl)-benzyl-alcohol, HCl (QH25).
The bronchodilator effect of QH25 (3-(4-methoxybenzylamino)-4-hydroxy-alpha-(tert. butylaminomethyl)benzylalcohol, HCl) a new beta2-adrenergic bronchodilator has been investigated in conscious guinea pigs and in anaesthetized guinea pigs and cats and compared to that of salbutamol and isoprenaline. In anaesthetized guinea pigs QH25 and isoprenaline were equipotent after intravenous administration, whereas salbutamol was four times less active. The same difference between QH25 and salbutamol was observed after intraduodenal administration. After oral administration in conscious guinea pigs QH25 was eight and five times more potent than salbutamol and isoprenaline respectively, whereas no difference was observed when the agents were administered as aerosols. The bronchodilator action of QH25 was apprxomately three times that of salbutamol in egg-albumine sensitized guinea pigs after oral administration. In anaesthetized cats the bronchodilator potency of QH25 was three times that of salbutamol and the same or slightly higher than that of isoprenaline. A half-life of 4 hours for the bronchodilator action in guinea pigs was determined for both QH25 and salbutamol after oral administration. The effect of QH25 and salbutamol on cardiovascular parameters i.e. chrono- and inotropic action and blood pressure decreasing effect in guinea pigs, cats and dogs was essentially the same whereas isoprenaline was from 5 to 30 times more potent. The potential tremorogenic action of QH25 estimated on the cat soleus muscle was eight times less than that of isoprenaline and the same or slightly less than that of salbutamol. From the experimental data it is concluded that QH25 has the same potency as isoprenaline as a bronchodilator agent but is more potent than salbutamol. Taking into account that isoprenaline is considerably more active on cardiovascular parameters and on the cat soleus muscle than QH25 which has the same or less effect than salbutamol on these parameters the data suggest that QH25 is a more selective bronchodilator agent than both isoprenaline and salbutamol.
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000420:Albuterol / Q000494:pharmacology; D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002415:Cats; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D013618:Tachyphylaxis
D001993:Bronchodilator Agents; D004983:Ethanolamines; D010627:Phenethylamines; D006632:Histamine; D007545:Isoproterenol; D000109:Acetylcholine; D000420:Albuterol