Analgesic activity of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide in mice and rats.
The potency of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide, which have the immunoadjuvant and immunomodulatory activity on pain threshold was studied. Two different analgesiometric procedures were employed: hot plate test and acetic acid writhing test in mice and rats. Both compounds were injected intravenously (1-4 mg/kg), intraperitoneally (5-50 mg/kg) and intracerebroventricularly (0.5-4 mg/kg) and were able to produce mild transient analgesia in both species. Writhing response was more influenced after systemic administration of drugs while hot plate latencies was not. On the contrary, latencies in hot plate test were more affected than the writhing response after intracerebroventricular administration. Dose response curve showed a bell shaped feature typical for peptides. Pretreatment with naltrexone, an opiate antagonist, did not prevent the analgesic action of tested compounds. The hyperalgesia induced by administration of parachlorophenylalanine, a serotonin depletor, could be prevented by administration of a nonanalgesic dose of MDP (0.025 mg/kg). At higher dosages (1 mg/kg) MDP was able to antagonize also general toxic effects of pCPA. These results support the possibility of participation of central serotonergic structures in MDP and AdDP induced analgesia. The peripheral mechanism of action, however, can not be completely ruled out.
Horák
P
P
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague.
Masek
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000547:Amantadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013045:Species Specificity
D000700:Analgesics; D004151:Dipeptides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine; D010134:Fenclonine