Imipramine inhibits intrathecal substance P-induced behavior and blocks spinal cord substance P receptors in mice

Autor: Tatsuro Iwashita, Takao Shimizu
Rok vydání: 1992
Předmět:
Zdroj: Brain Research. 581:59-66
ISSN: 0006-8993
DOI: 10.1016/0006-8993(92)90344-9
Popis: The mechanism of the antinociceptive effect of the tricyclic antidepressant imipramine was investigated in mice. Intrathecal (i.t.) administration of imipramine produced dose-dependent antinociception in the tail-pinch and tail-flick tests with ED50 values (95% confidence limit) of 27.5 (17.0–43.9) and 20.2 (12.6–32.2) nmol, respectively. In substance P (SP)-induced nociceptive behavior, imipramine (i.t.) also produced dose-dependent antinociception with ED50 value of 20.2 (16.1–25.2) nmol. Tissue concentration of imipramine was between 55.2 and 104.4 nmol/g tissue when these ED50 values of imipramine were i.t. administered. In the SP-induced behavior, the antinociceptive effect of 31.6 nmol of imipramine was not antagonized by the α-adrenergic receptor antagonist phentolamine, the serotonergic receptor antagonist methysergide, or the opioid receptor antagonist naloxone. In vitro study, imipramine dose-dependently inhibited specific [3H]SP binding in the spinal cord homogenate wiith IC50 value of 2.37 × 10−4M and this value corresponds to 8.6 μmol/g tissue concentration. These data indicate that imipramine produces antinociceptive effect at about 100 times lower dose than SP receptor blockade.
Databáze: OpenAIRE