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Serotonin enhances oxybuprocaine- and proxymetacaine-induced cutaneous analgesia in rats.

Chou, An-Kuo; Chiu, Chong-Chi; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia.
Eur J Pharmacol ; 846: 73-78, 2019 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-30639797
The aim of the study was to investigate the analgesic effects of adding serotonin to oxybuprocaine or proxymetacaine preparations. We employed a rat model of the cutaneous trunci muscle reflex (CTMR) to conduct the dose-response curves and duration of drugs (oxybuprocaine, proxymetacaine, or serotonin) as an infiltrative anesthetic. The use of isobolographic methods to analyze the drug-drug interactions. We showed that oxybuprocaine and proxymetacaine, as well as serotonin produced dose-dependent skin antinociception. On the basis of 50% effective dose (ED50), the rank order of drug potency was serotonin [7.22 (6.45-8.09) µmol/kg] < oxybuprocaine [1.03 (0.93-1.15) µmol/kg] < proxymetacaine [0.59 (0.53-0.66) µmol/kg] (P < 0.01 for each comparison). The sensory block duration of serotonin was longer (P < 0.01) than that of oxybuprocaine or proxymetacaine at the equipotent doses (ED25, ED50, and ED75). The mixture of serotonin with oxybuprocaine or proxymetacaine produced a better analgesic effect than the drug itself. We have concluded that oxybuprocaine, proxymetacaine, or serotonin displays dose-related cutaneous analgesia. Oxybuprocaine or proxymetacaine is more potent and has a shorter duration of cutaneous analgesia than serotonin. Serotonin produces a synergistic antinociceptive interaction with oxybuprocaine or proxymetacaine.