Antinociceptive action of bradykinin and related kinins of larger molecular weights by the intraventricular route.

1. It was shown previously that bradykinin (Bk) when given intraventricularly increases the threshold of electrical stimulation of dental pulp in the rabbit.2. Bradykinin derivatives with increasing molecular weights (lysyl-Bk (L-Bk), methionyl-lysyl-Bk (ML-Bk) and glycyl-arginyl-methionyl-lysyl-Bk (GAML-Bk)) were found to produce effects of decreasing intensity on the threshold of electrical stimulation according to the following scale: Bk (1.00)>L-Bk (0.28)>ML-Bk (0.060)>GAML-Bk (0.047).3. The four peptides had similar relative activities on the guinea-pig ileum but an inverse relationship in their effects on vascular permeability and rat blood pressure.4. The discrimination index, increase in vascular permeability/antinociceptive effect rose to values of the order of 170 to 550, taking Bk as the reference peptide (potency=1.00).5. We conclude that the increase in threshold of electrical stimulation could not be due to an increase in vascular permeability or decrease of blood pressure.