Effect of monoamine-related drugs on inhibitory action of difenamizole to acetic acid-induced writhing in mice

Effects of drugs that modify tryptaminergic or catecholaminergic mechanisms were determined in mice regarding the analgesic action of difenamizole and morphine. Analgesia was assessed by the writhing movements induced by acetic acid in mice. The following monoamine-related drugs were given at doses which hardly influence the writhing: 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), p-chlorophenylalanine (p-CPA), 5, 6-dihydroxytryptamine (5, 6-DHT), L-DOPA, dopamine (DA), norepinephrine (NE), methamphetamine, α-methyl-p-tyrosine (α-MT), 6-hydroxydopamine (6-OHDA), diethyldithiocarbamate (DDC), phenoxybenzamine and reserpine. 5-HTP (25 mg/kg, p.o.) and 5, 6-DHT (25 µg/mouse, i.c.) significantly antagonized the analgesic action of difenamizole, but other 5-HT-related drugs did not significantly influence the action of this analgesic. The analgesic action of difenamizole was also antagonized by DA (2.5 and 5.0 µg/mouse, i.c.) but was significantly potentiated by 6-OHDA (50 and 100 µg/mouse, i.c.), phenoxybenzamine (5 and 10 mg/kg, s.c.) and reserpine (1.5 and 2 mg/kg, i.p.). NE (2.5 and 5.0 µg/mouse, i.c.) and DDC (50 mg/kg, s.c.) did not influence the effect of difenamizole. 5-HTP (50 mg/kg), 5-HT (1.0 µg/mouse, i.c.) and NE (2.5 and 5.0 µg/mouse, i.c.) significantly potentiated the analgesic action of morphine, but 5, 6-DHT (25 µg/mouse, i.c.) and 6-OHDA (50 µg/mouse, i.c.) significantly antagonized the effect of this narcotic. The effect of this drug was not significantly modified by pretreatment with other monoamine-related drugs. These results suggest that the analgesic action of difenamizole may be related to DA, but the effect of morphine may be mediated by 5-HT and NE. The biogenic amines may play a different role depending on the type of analgesic.