Phenothiazine-type antipsychotics elicit cutaneous analgesia in rats.
BACKGROUND
Local anesthetics exert their anesthetic and analgesic effects by blocking the sodium channels in the nervous system. Phenothiazine-type antipsychotics also block sodium channels, but the local anesthetic characteristics of these drugs have not been evaluated. The aim of this study was to evaluate the cutaneous analgesic effect of phenothiazine-type antipsychotics.


METHODS
Using a subcutaneous injection model in rats, we tested the cutaneous analgesic effects of six phenothiazine-type antipsychotics (mesoridazine, promazine, chlorpromazine, fluphenazine, perphenazine and triflupromazine) at a dose of 0.6 mumol, and compared them with those of bupivacaine and lidocaine. A saline injection was used as the control.


RESULTS
All six phenothiazine-type antipsychotics elicited cutaneous analgesia. At the dose of 0.6 mumol, the potencies of mesoridazine and promazine were similar to that of bupivacaine; the other four drugs were less potent (p<0.001 for each comparison). Mesoridazine had a longer duration of action than bupivacaine (p<0.001). In terms of ED(50) values, mesoridazine was more potent and longer-acting than bupivacaine and lidocaine (p<0.01 for each comparison).


CONCLUSIONS
Of the antipsychotic drugs tested, mesoridazine is potentially the best candidate for development into a potent, long-acting local anesthetic. However, toxicity studies are needed before these agents can be used clinically as analgesics.
Chen
Yu-Wen
YW
Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan, R.O.C.
Chu
Chin-Chen
CC
Chu
Koung-Shing
KS
Shieh
Ja-Ping
JP
Chien
Chih-Chiang
CC
Wang
Jhi-Joung
JJ
Kao
Cheng-Hsing
CH
D000698:Analgesia; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology
D000779:Anesthetics, Local; D014150:Antipsychotic Agents; D010640:Phenothiazines; D026941:Sodium Channel Blockers