Pharmacological properties of a new antiasthmatic xanthine derivative devoid of central stimulatory activity.
The bronchodilating effect and other related pharmacological properties of an 8-amino alkyl substituted xanthine (S 9795) were compared with those of reference drugs, in particular theophylline. The in vitro studies using the tracheal ring, taenia coli, rat peritoneal mastocytes and enzymic preparations demonstrated the potency of S 9795 as an antiasthmatic drug, possessing protective activity superior to that of theophylline and enprofylline. S 9797 was 100 times more active as a cAMP phosphodiesterase inhibitor than theophylline. The compound also protected against mast cell degranulation and consequent release of spasmogen due to antigen-antibody reaction or induced by Ca2+ movements. Given orally or intravenously. S 9795 had a highly selective protective effect against bronchoconstriction induced by pharmacological reagents or allergic reactions with no demonstrable effect on the central nervous or cardiovascular systems. The pharmacological effects of S 9795 were of longer duration than those of theophylline and enprofylline. These studies demonstrate the potential therapeutic value of S 9795 in the therapy of bronchospastic disorders.
Duhault
J
J
Institut de Recherches Servier, Suresnes, France.
Boulanger
M
M
Lonchampt
M
M
Tisserand
F
F
Holstorp
S
S
Saint-Romas
G
G
Pennel
L
L
Regnier
G
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use; D014132:Trachea / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use
D001993:Bronchodilator Agents; D014970:Xanthines; C055633:S 9795; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases