ABSTRACT
A series of substituted 11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated as antiallergy agents. Several analogues were orally active. 2-Methyl-11-oxo-11H-pyrido[2,1-b]quinoazoline-8-carboxylic acid (6) was superior to cromolyn sodium and doxantrazole orally and intravenously in the rat PCA test and a rat allergic bronchospasm model.
Subject(s)
Hypersensitivity/drug therapy , Quinazolines/chemical synthesis , Animals , Bronchial Spasm/drug therapy , Bronchial Spasm/immunology , Bronchial Spasm/physiopathology , Histamine Release/drug effects , In Vitro Techniques , Mast Cells/drug effects , Mast Cells/immunology , Passive Cutaneous Anaphylaxis/drug effects , Pulmonary Ventilation/drug effects , Quinazolines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
Pregnancies in hamsters may be terminated by 10 mug PGF2alpha administered b.i.d. on days 4, k and 6 of gestation. Small (250 mug and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 mug of estrone essentially normalized the gestation; administration of PGF2alpha at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F2alpha on pregnancy in hamsters.
