Abstract：
: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 alpha-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 with IC50 value of 2.37 x 10(-4) M and this value corresponds to 8.6 mumol/g tissue concentration. These data indicate that imipramine produces antinociceptive effect at about 100 times lower dose than SP receptor blockade.
journal_name
Brain Resjournal_title
Brain researchauthors
Iwashita T,Shimizu Tdoi
10.1016/0006-8993(92)90344-9subject
Has Abstractpub_date
1992-05-22 00:00:00pages
59-66issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(92)90344-9journal_volume
581pub_type
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