Relationship between biogenic amines and analgesic action of difenamizole in heat induced reflexes

Effects of drugs that modify catecholaminergic or tryptaminergic mechanisms were determined in experimental animals regarding the analgesic action of difenamizole, morphine, and aminopyrine. Analgesia was assessed by the hot plate method in mice and the hot water induced tail withdrawal reflex in rats. Both 5-hy-droxytryptophan(5-HTP) and L-dopa potentiated the analgesic action of morphine, but antagonized the action of difenamizole in the hot plate test. p-Chlorophenylalanine(pCPA), α-methyl-p-tyrosine (α-MT), and reserpine antagonized the effect of morphine as assessed by this same test. α-MT potentiated the analgesic action of difenamizole. The analgesic action of aminopyrine was hardly modified in the hot plate method by pretreatment with 5-HTP, pCPA, L-dopa, and α-MT. In rats, 5-HTP antagonized the effect of morphine, while pCPA, L-dopa, and α-MT caused no appreciable change in the analgesic action of morphine in the hot water induced tail withdrawal reflex. The effect of difenamizole was not modified by pretreatment with these monoamine-related drugs. On the other hand, brain 5-hydroxytryptamine content was increased by pretreatment with 5-HTP in both tests. These results suggest that the analgesic action of difenamizole and morphine, as measured in the hot plate test in mice, may be mediated by catecholamines and 5-hydroxytryp-tamine, but that other mechanisms may be involved in the hot water induced tail withdrawal reflex in rats. In addition, the biogenic amines may play a different role depending on the type of analgesic.