Neural actions of several substance P antagonists in the rat spinal cord.
Four substance P (SP) antagonists were tested on anaesthetized rats, by injecting 8 microgram amounts into the spinal cord (T8-T9), and by observing their effects on the hypothalamo-neurohypophysial responses to a presumably painful stimulus, the superfusion of the hepatic portal vein with 1 microM bradykinin. Only two antagonists, the new D-Pro4,D-Trp7,9,10,Val8-SP4-11 and D-Pro4,D-Trp7,9,10-SP4-11 were capable of inhibiting the responses by 50-60%, the former compound having 3 times less agonistic activity. The results suggest that substitution of the aromatic phenylalanine by the non-polar valine in position 8 may significantly improve the overall characteristics of neurally active SP antagonists.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D013373:Substance P; D001920:Bradykinin