Comparison of nonivamide and capsaicin with regard to their pharmacokinetics and effects on sensory neurons.
Nonanoyl vanillylamide (nonivamide NVA) was compared with trans-8-methyl-N-vanillyl-nonenamide (capsaicin, CAP) with regard to their pharmacokinetic properties, their potency in stimulating primary afferent neurons and depleting them of substance P and somatostatin in rats. Following the injection of 50 mg kg-1 the time course of the presence of NVA in brain and blood was similar to that of CAP. The concentration of NVA in brain was higher than in blood; the reverse was true for CAP. The ability of NVA and CAP to stimulate afferent neurons was measured by the reflex depressor response following i.v. injection and by the number of wiping movements following instillation of the substances into the eye. In both tests, the potency of NVA was about half of that of CAP. Treatment of newborn rats by s.c. injections of 50 mg kg-1 NVA or CAP seemed to cause a larger depletion of substance P and somatostatin in the sciatic nerve and the spinal cord than treatment of adult rats. Depletion by CAP was generally larger than that by NVA although depletion experiments are hardly suitable for quantification. The depletion of substance P by CAP and NVA could be correlated with the extent to which ocular chemosensitivity and neurogenic plasma extravasations were attenuated. The methods used are discussed in view of their possible use in screening further capsaicin analogues.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives; D005123:Eye / Q000187:drug effects; D005260:Female; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014641:Vanillic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D062385:Hydroxybenzoates; D013373:Substance P; D013004:Somatostatin; D014641:Vanillic Acid; D002211:Capsaicin; C040937:nonivamide