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

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.

Skin nociceptive block with pramoxine delivery by subcutaneous injection in rats.

BACKGROUND: Pramoxine has been shown to produce spinal anesthesia, while cutaneous analgesia (peripheral) of pramoxine is not established. The experimental goal was to examine cutaneous antinociception produced by a local anesthetic (LA) pramoxine and compare this result with that of another well-known LA lidocaine. METHODS: Cutaneous antinociception was evaluated by blockade of pinprick- induced cutaneous trunci muscle reflex (CTMR) on the skin of rat's back. After the dose-related curves were constructed, the quality and duration of drug's (lidocaine and pramoxine) cutaneous antinociception were compared. RESULTS: We showed that pramoxine, as well as lidocaine produced skin antinociception in a dose-related fashion. The relative potency (ED50 [50% effective dose] basis) was lidocaine (5.44 [4.67-6.35] µmol) greater than pramoxine (42.1 [38.8-45.7] µmol) (p < 0.01). On the basis of equianalgesic doses (ED75, ED50, and ED25), pramoxine caused equivalent duration of cutaneous antinociception to lidocaine. CONCLUSIONS: These preclinical data indicated that pramoxine elicits skin antinociception dose-relatedly. Pramoxine exhibits a potency less than that of lidocaine while they have a comparable duration of skin antinociceptive action.