Studies on alkyl-xanthine derivatives. II. Pharmacokinetic and pharmacodynamic studies of a new bronchodilator, 1-methyl-3-propylxanthine(MPX).

概要

論文の詳細を見る
A new xanthine derivative bronchodilator, 1-methyl-3-propylxanthine (MPX), and 1-methyl-3-butylxanthine (MBX) were synthesized. We evaluated their relaxant effects on tracheal smooth muscle isolated from guinea pigs and pharmacokinetic characteristics in rats using 1, 3-dimethylxanthine (theophylline, TPH) as the reference drug. Dose-dependent relaxant effects were observed in the concentration range of 1 × 10<SUP>-6</SUP> to 1 × 10<SUP>-4</SUP> M, and both MPX and MBX exert very much stronger relaxant effects than TPH with nearly equal potency. There were significant differences in the pharmacokinetic and physico-chemical properties among these drugs, both MPX and MBX having shorter half-lives, higher plasma protein binding in vivo and stronger hydrophobicity compared to TPH. The present study suggested that the N3-alkyl chain length is significant for increasing the relaxant effect and affecting the pharmacokinetic and physico-chemical properties of these drugs.
公益社団法人日本薬理学会の論文