Comparison of Some New Analgesic Compounds

Abstract

A study of 6 new analgesic agents and a comparison of them with demerol and compd. 10820 is presented. Analgesic action was detd. in rats by the method of Haffner and in dogs and man by the thermal radiation method. In rats and dogs, the substs. were given by intraper. injn., and in man, by mouth. The 6 compds. (10820, 10446, 10582, 10581, 10819, 10720) were more active analgesieally than demerol in rats, dogs, and man. Compd. 10446 had the same potency as demerol in dogs, but was more effective in rats and man. An OH-group at metaposition in the benzene nucleus (10446) increased the analgesic action of demerol. The ketone form (10720) was more potent than the ester (10446). Compd. 10726 caused severe vomiting. Analgesic potency and acute toxicity paralleled each other but the effects on blood pressure of anesthetized dogs showed marked differences. Marked fall of blood pressure followed injn. of demerol derivatives, except for 10726. The depressor effects of diphenyl compds. were less marked. Cardioinhibition resulted from the di-phenyls, but only 1 demerol subst. (10720) produced this effect. Stimulation of respiration occurred with the esters and depression with the ketones. Inhibition of salivary secretion occurred with the esters whereas the ketones produced much less effect. Four new compds. were tested on man along with demerol and 10820. With threshold doses, the most frequent symptom was lightheadedness, the intensity of which varied with the degree of analgesia.