The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms.
Antinociceptive effects of various neuroleptics in animal acute pain-models have been described, mediated trough different pathways including the opioid system. In this study, we assessed the antinociceptive effects of the atypical neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2 and D3 receptors. Furthermore, at low doses amisulpride has a selective preference for presynaptic dopamine autoreceptors, while at high doses it manifests a preferential action at post-synaptic dopamine receptors. We found amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay, with an ED50 of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05), indicating an involvement of opioid mechanisms as mediators of the antinociceptive effect of amisulpride. Beta-funaltrexamine (mu1- and mu2-opioid receptor antagonist), naloxonazine (selective mu1-opioid receptor antagonist), naltrindole (selective delta-opioid receptor antagonist), Nor-binaltorphamine (kappa1-opioid receptor antagonist) reversed amisulpride antinociception at the same dose that they antagonized morphine's antinociceptive effect (all P<0.005). We found that the sensitivity of amisulpride-induced antinociception is mediated through selective involvement of all three opioid receptor subtypes. Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites.
Department of Psychiatry, Tel Aviv Sourasky Medical Center and Tel-Aviv University Sackler School of Medicine, Tel Aviv 64239, Israel.
Tal
T
Weizman
Chaim G
CG
Pick
Maria M
MM
Backer
Tova
T
Rigai
Miki
M
Bloch
Shaul
S
Schreiber
D000077582:Amisulpride; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000700:Analgesics; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D013469:Sulpiride; D000077582:Amisulpride