Traxanox was inactive against classic acute and subacute inflammation models such as carrageenin paw edema, UV erythema, 6-hr Evans blue-carrageenin (E-C) pleurisy and cotton pellet granuloma formation, and it failed to inhibit the production of prostaglandin E₂ and a slow reacting substance from rat peritoneal leucocytes which phagocytize killed bacteria in vitro. On the other hand, traxanox inhibited the anaphylactoid reaction and decreased the pleural fluid in 24-hr E-C pleurisy. Traxanox (100 mg/kg, p.o.) also showed a tendency to suppress dextran edema and cotton pellet granuloma formation in adjuvant arthritis (AA) in rats. In experimental models of delayed type hypersensitivity (DTH), traxanox (100 mg/kg, p.o.) inhibited the accumulation of the exudate and the leucocyte migration in B. pertussis-induced pleurisy in rats. Traxanox (50 mg/kg) did not show any effect on AA in Lewis rats when administered orally for 21 days after the adjuvant inoculation, but the combined administration of traxanox with hydrocortisone (10 mg/kg, p.o.) or indomethacin (0.25 mg/kg, p.o.) resulted in a synergistic inhibition of AA. When the administration of traxanox was started 21 days before the adjuvant inoculation, it inhibited AA in a dose-dependent manner (50 ?? 100 mg/kg, p.o.). On the other hand, traxanox (100 mg/kg, p.o.) enhanced the concanavalin A-induced DTH-like skin reaction in guinea pigs. These results indicate that the mode of action of traxanox on inflammatory responses resembles that of D-penicillamine or levamisole, so that it may prove to be clinically effective in treating rheumatoid arthritis.

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Antihypertensive effects of pinacidil (PND) were compared with those of hydralazine (HDL) and nifedipine (NFD) by determining the systolic blood pressure of the caudal arteries of conscious SHR and desoxycorticosterone (DOC)/saline hypertensive rats at temperatures between 29°C to 30°C using a newly developed tail cuff method. 1) A dose dependent antihypertensive effect of PND in male SHR was observed in a dose exceeding 1 mg/kg, p.o. Comparison of antihypertensive effects during 6 hr after oral administration of antihypertensive agents showed that relative potencies of HDL and NFD to PND (1.0) were approximately 0.8 and 0.3, respectively. 2) Although no difference was observed in the antihypertensive effect of HDL between male and female SHR, these effects by PND and NFD were more potent in female SHR. 3) No tolerance was observed in the antihypertensive effect of PND by the once a day oral administration for 5 weeks in male SHR and DOC/saline hypertensive rats. Dose-dependent antihypertensive effects of PND in doses above 1 mg/kg were always observed during experimental periods. 4) In spite of the potent antihypertensive effects, pathological changes such as hyperplasia and hyalinization of arterial walls in kidneys in DOC/saline hypertensive rats were not improved by continuous administration of PND or HDL.

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Effects of combined administration of pentoxifylline (PTX) and precursors of 5-hydroxytryptamine (5-HT) on behavior and cerebral contents of 5-hydroxytryptophan (5-HTP), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were examined in mice. The intraperitoneal administration of PTX at 100 mg/kg to mice pretreated with pargyline (100 mg/kg, i.p.) significantly increased the frequency of head twitches induced by 5-HTP (25 mg/kg, i.p.), and the effect of PTX was approximately 2 times more potent than that of other methylxanthines. In these mice, the cerebral contents of 5-HTP, 5-HT and 5-HIAA were also elevated significantly. However, PTX itself had no effect to induce head twitch response or to increase the contents of the indoles in mice. When administered in combination with tryptophan (100 mg/kg, i.v.) to pargyline-pretreated mice, PTX (100 mg/kg, i.p.) did not affect the contents of the indoles in the brain. These results suggest that PTX may have an effect to promote transport of exogenous 5-HTP into the neurons, besides the 5-HT turnover-increasing effect common to methylxanthine derivatives.

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