Antidepressants and opiates interactions: pharmacological and biochemical evidences

Imipramine, chronically administered to rats (20 mg/Kg/day X 20) has a potent analgesic effect per se (hot plate test), increases morphine analgesia and intensifies morphine withdrawal syndrome precipitated by naloxone. Receptor binding studies performed with 3H-naloxone revealed that chronic administration of imipramine results in a marked increase of opiate binding sites in the brain. This increase persisted when the rats treated chronically with imipramine were rendered tolerant to morphine by s.c. implantation for 3 days of a pellet containing 100 mg of morphine. Since antidepressants exert their own analgesic effect, increase morphine analgesia and displace opiate receptor binding, it may be that by interacting with the opiate receptor complex imipramine induces supersensitivity in opiate recognition binding sites.