Abdallah, A.H., J.W. Burnell, and R.J. Cregge: Comparative evaluation of the relaxant effects of MDL-257, its metabolites, and some related compounds on guinea pig tracheal cylindrical segments. Drug Dev. Res. 7:185-193, 1986. The smooth muscle relaxant activities of pyridazine], a new, nonsympathomimetic bronchodilator, its metabolites (in man and rats), and some related compounds were compared to that of aminophylline in guinea pig tracheal cylindrical segments. The lC50 of MDL-257 against KCI-, histamine-, acetylcholine, and 5-hydroxytryptamine-induced contractions were 5.2 x 5.3 x 9.1 x and 1.4 x l o w 5 M, respectively. The relaxant activity of aminophylline was equal to that of MDL-257 against all of the spasmogens studied. Dihydroxy substitution on the piperidine ring of MDL-257 reduced its relaxant activity against KCI, histamine, and 5-hydroxytryptamine 25-43-fold and its activity against acetylcholine was almost abolished. The monohydroxy and the amino alcohol metabolites of MDL-257 were two to 20 times less potent than the parent compound and their activities against acetylcholine-induced contractions were minimal. The acidic metabolites of MDL-257 exhibited very weak activity against all of the spasmogens tested.