Inhibitory effect of a pyrrolizidine alkaloid, crotalaburnine, on rat paw oedema and cotton pellet granuloma.

1 The anti-inflammatory activity of crotalaburnine (=anacrotine) was investigated against increased vascular permeability and oedema produced by formalin, carrageenin, hyaluronidase, 5-hydroxytryptamine, dextran, bradykinin and prostaglandin, and against formation of granulation tissues by cotton-pellet in rats. The effect was compared with the activity of hydrocortisone, phenylbutazone, sodium salicylate and cyproheptadine against different types of inflammation.2 Crotalaburnine (40 mg/kg s.c. x 5 alternate days) had no significant inhibitory effect against formalin-induced arthritis, while hydrocortisone (40 mg/kg s.c. x 10 days) was effective from the fifth day onwards.3 Against carrageenin-induced oedema both crotalaburnine (10 mg/kg s.c.) and phenylbutazone (100 mg/kg oral) produced a similar degree of inhibition. Hydrocortisone (10 mg/kg s.c.) produced slightly greater inhibition.4 In normal rats crotalaburnine (10 mg/kg s.c.), phenylbutazone (100 mg/kg oral) and sodium salicylate (500 mg/kg i.p.) inhibited hyaluronidase-induced oedema. However, in adrenalectomized rats, there was a reduction of the inhibitory effect of sodium salicylate but not of phenylbutazone or crotalaburnine.5 Crotalaburnine (40 mg/kg s.c. and 30 mg/kg i.p., respectively) was ineffective against 5-hydroxytryptamine- and dextran-induced oedema but against bradykinin- and prostaglandin-induced oedema (in a dose of 20 mg/kg i.p.) it was quite effective. In a parallel series cyproheptadine (10 mg/kg oral and i.p., respectively) produced significant inhibition of 5-hydroxytryptamine- and dextran-induced oedema, while phenylbutazone (100 mg/kg i.p.) failed to produce any significant inhibition of prostaglandin-induced oedema.6 Against cotton-pellet granuloma crotalaburnine, in half the dose of hydrocortisone, produced similar inhibition while phenylbutazone produced much greater inhibition in five times the dose of crotalaburnine given orally.7 The possible mode of action of crotalaburnine as an anti-oedema agent is discussed.