Pharmacological activities of glycyrrhetinic acid derivatives: analgesic and anti-type IV allergic effects.

Glycyrrhetinic acid (Ia) and fourteen derivatives of glycyrrhetinic acid were examined to estimate the antinociceptive activity (tests on writhing and vascular permeability induced by 0.7% acetic acid) and anti-type IV allergic effects in mice. Among them, three dihemiphthalate compounds (IIf, IIIc, IVc) derived from, deoxoglycyrrhetol (IIa), showed strong inhibition of writhing and dye leakage at a dose of 6.25 mg/kg (p.o.) and type IV allergy at 25 mg/kg (i.p.). Among the hemisuccinate compounds, Ib, IIb and IIIb, had significant inhibitory effects on both writhing and vascular permeability, whereas IIc and IVb inhibited only one of the two responses, at 200 mg/kg (p.o.). Four of the hemisuccinate compounds (IIb, c, IIIb, IVb) suppressed type IV allergy at 100 mg/kg (i.p.). Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa) showed no detectable inhibition in the screening tests at doses of less than 200 mg/kg (i.p.).