Effect of iprindole on the metabolism of trimipramine in the rat.
Major metabolites of trimipramine in young male Sprague-Dawley rats are the result of alicyclic and aromatic ring oxidation. The four major urinary metabolites have been identified as 10-oxotrimipramine, 2-hydroxytrimipramine, 2-hydroxynortrimipramine, and 2-hydroxy-10-oxotrimipramine. When iprindole was administered to rats prior to trimipramine, the effect on trimipramine metabolism was profound. The formation of both 10-oxo metabolites was virtually completely inhibited; the production of 2-hydroxytrimipramine was significantly reduced while the metabolic formation of 2-hydroxynortrimipramine was increased. It is apparent from these preliminary results that metabolic alicyclic and aromatic hydroxylations are catalyzed by different cytochrome P450 isozymes and more than one P450 isozyme is involved in the aromatic ring oxidation of trimipramine and nortrimipramine. (+info)
Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine.
Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients.
A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression. (+info)
An increase in sensitivity of rat cingulate cortical neurones to substance P occurs following withdrawal of chronic administration of antidepressant drugs.
The sensitivity of neurones in the cingulate cortex of the rat to iontophoretically applied substance P (SP) was tested one hour after a single dose of various antidepressant drugs and also 1 day following the termination of a chronic dosing schedule (14 once daily injections) of the same agents. One hour after a single injection of desipramine (DMI), chlorimipramine (CMI), trimipramine (TMI) or zimelidine ( ZIM ) (all at 10 mg kg-1 i.p.) there was no change in the mean size of excitatory responses to SP compared to those before the injection. There was a tendency towards a decrease in the TMI group. One day following the last of 14 consecutive daily injections (10 mg kg-1 i.p.) of the above agents there was a significant increase in the size of excitatory responses to SP compared to those in rats receiving daily saline injections. However, 14 days of treatment with DMI did not alter the responses to L-glutamate. Similar chronic dosing schedules with either diazepam (5 mg kg-1) or fluphenazine (5 mg kg-1) did not affect the responses to SP. Thus chronic but not acute administration of antidepressant drugs results in an increase in the sensitivity of neurones, in the cingulate cortex of the rat, to SP. (+info)
Antiulcer effects of trimipramine using various laboratory models.
Trimipramine, a tricyclic antidepressant, significantly inhibited the development of experimental gastric ulcers induced by various methods like stress, drug (aspirin, reserpine) and Shay's pyloric ligation in an inbred strain of albino rats. Although similar protection was observed with cimetidine, it was found to be ineffective against reserpine-induced ulcers. The antisecretory and ulcer protective effects were not only comparable with that of cimetidine, but even superior in the case of reserpine-induced ulcers. The ability of trimipramine to reduce the ulcer index in various experimental models suggests a centrally mediated effect. Trimipramine appears to be a potentially useful additional therapeutic agent not only because of its anti-ulcer property, but also due to its antidepressive property. (+info)
Clinical trial value of trimipramine versus placebo in duodenal ulcer healing.
Thirty-two patients with duodenal ulceration took trimipramine 50 mg or placebo. Fifteen patients on each treatment completed the study. Endoscopy at four weeks showed ulcer healing in seven (46%) patients on trimipramine, compared with only two (15%) on placebo (P less than 0.05). However, by eight weeks there were eight (53%) patients in both groups with healed ulcers. There were no significant differences between the two groups in ulcer symptoms. Drowsiness was reported by eight patients on trimipramine compared with only one on placebo. Trimipramine 50 mg appears to increase the rate of ulcer healing in the short term. Side-effects at the dose used may limit its long-term usefulness. (+info)