Synergistic Effects of Serotonin or Dopamine Combined With Lidocaine at Producing Nociceptive Block in Rats.

Abstract

The purpose of this experiment was to investigate the interactions of the local anesthetic lidocaine combined with an agent (serotonin or dopamine) as infiltrative anesthetics. Cutaneous analgesia was characterized by the blockade of the cutaneous trunci muscle reflex following 6 skin pinpricks on the rat back. Serotonin or dopamine at producing cutaneous analgesia in a dosage-dependent fashion was compared with lidocaine. Drug-drug interactions were calculated using the isobolographic analysis. We revealed that serotonin, dopamine, and lidocaine provoked dose-related cutaneous analgesic effects. On the 50% effective dose basis, the rank of drugs' potency was found to be serotonin (1.70 [1.56-1.85] μmol) > lidocaine (5.18 [4.67-5.75] μmol) > dopamine (43.0 [40.9-45.2] μmol) (P < 0.01). At doses equivalent to their 25%, 50%, and 75% effective doses, serotonin or dopamine elicited a longer duration of action than lidocaine (P < 0.01) on producing cutaneous analgesia. Coadministration of serotonin or dopamine with lidocaine produced a synergistic effect. The preclinical data showed that serotonin and dopamine produce dose-related cutaneous analgesic effects as an infiltrative anesthetic. Serotonin has a better potency with a much longer duration of action compared with lidocaine at provoking cutaneous analgesia. Serotonin or dopamine as an adjuvant increases the quality of lidocaine in cutaneous analgesia.