Desipramine versus ropivacaine for prolonged cutaneous analgesia in rats

ABSTRACT

Desipramine is a tricyclic anti depressant that has a potent local anesthetic activity comparable to ropivacaine. In keeping with the objective of identifying drugs for prolonged cutaneous analgesia, we compared the cutanaous analgesic effectiveness of desipramine and ropivacaine in rats. Rats were subcutaneously injected in shaved dorsal skin. The skin wheal raised after injection of 0.6 ml of various concentrations of either desipramine or ropivacaine with and without epinephrine 1,200,000 was marked. Inhibition of the Cutaneous trunci muscle reflex was evaluated quantitatively by the fraction of times a total of six pinpricks applied to the marked area failed to elicit a nocifensive motor response compared with control responses. No responses out of six pinpricks was defined as 100% maximum possible effect. Complete recovery from the cutaneous analgesia elicited by 0.05% and 0.5 desipramine versus 0.05% and 0.5- ropivacaine occurred in 9.7 +/- 0.2 and 19,3 +/- 0.4 versus 2.2 +/- 0.1 and 16.1 +/- 0.2h, respectively [Mean +/- SE]. Addition of epincphrine increase this duration to 14.1 +/- 0.1 and 21.4 +/- 0.2 versus 3.2 +/- 0.1 and 17.0 +/- 0.3 h, respectively. Complete nociceptive blockade after coinjection of 0.25%, desipramine 0.25% ropivacainc and epinephrine lasted 24 +/- 0.5 h, and complete recovery from this block took 33 +/- 0.5 h. Areas under the percent maximum possible effect [MPE] versus time curve were 1.77 +/- 0.24 and 1.47 +/- 0.5% h for 0.5% desipramine and ropivacaine with epinephrine, respectively, and this value was 2.83 +/- 0.62 h. for the coinjected 0.25% desipramine, 0.25 ropivacaine, and epinephrine admixture. Desipramine is a longer-acting local anesthetic [LA] compared with ropivacaine for cutaneous infiltration. Its analgesic effectiveness is significantly enhanced by epinephrine. Coinjection of desipramine and ropivacaine with epinephrine enhances the analgesic duration of both drugs