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PubMed1986

High affinity [3H]imipramine binding and serotonin uptake to platelets of adolescent females suffering from anorexia nervosa.

High affinity [3H]imipramine binding and [3H]serotonin uptake to platelets were investigated in 17 anorexic females aged 15-18 years as compared to 15 healthy females of similar ages. A significant decrease in the density of [3H]imipramine binding sites was observed in anorexics as compared to controls (368 +/- 40 vs 517 +/- 38 fmoles/mg protein, p less than 0.01). No alteration in Kd values or in the kinetic parameters of serotonin uptake (Vmax, Km) were noted. The fact that the decrease in imipramine binding is not accompanied by a parallel reduction in serotonin uptake might indicate that anorexia nervosa is not ultimately related to major depression and that the imipramine binding site is not identical to the serotonin uptake site.

Adolescent↗
PubMed1987

Clinical and treatment effects on 3H-clonidine and 3H-imipramine binding in elderly depressed patients.

3H-clonidine and 3H-imipramine binding were measured in depressed patients, 55 years and older. There was no significant difference in either 3H-clonidine or 3H-imipramine binding between depressed patients and age- and sex-matched controls. There was no significant correlation between 3H-clonidine or 3H-imipramine binding and severity of depression before treatment. There was a significant negative correlation between the KD of 3H-imipramine binding sites and Hamilton score over seven weeks of antidepressant treatment. There was no significant difference between receptor data of responders and nonresponders to antidepressant treatment.

Blood Platelets↗
PubMed1988

Different components of 3H-imipramine binding in rat brain membranes: relation to serotonin uptake sites.

In the present paper we confirm and extend previous studies showing heterogeneous 3H-imipramine (3H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM 3H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three 3H-IMI binding sites: two of these (high and low affinities) were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover, this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a closer relation to serotonin uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific 3H-IMI, may be of help in understanding its relation with serotonin uptake system.

Animals↗
PubMed1988

Interaction of some atypical antidepressants and adrenoceptor antagonists with imipramine: a behavioural study with isoprenaline-induced drinking.

The systemic administration of isoprenaline to rats produced a dose-dependent increase in drinking which was antagonized by propranolol. While oral administration of the antidepressant, imipramine, alone had no significant effect on this response, the increase was significantly inhibited by administration of imipramine together with each of the following drugs over a period of 4 days: bupropion (21.0 mg/kg/day, p.o.), a selective inhibitor of the uptake of dopamine and nomifensine (10.6 mg/kg/day, p.o.), a relatively selective dopamine and a blocker of the uptake of noradrenaline. Similarly, the combination of the selective alpha 1-adrenoceptor antagonist, prazosin (2.37 mg/kg/day, p.o.); the selective alpha 2-adrenoceptor antagonist, yohimbine (2.38 mg/kg/day, p.o.) or the non-selective alpha-adrenoceptor blocker, phentolamine (4.65 mg/kg/day, p.o.) with imipramine caused a significant inhibition of the isoprenaline-induced drinking. It is concluded that fast desensitization of central beta-adrenoceptors in the rat can be produced after the oral subacute simultaneous administration of imipramine with alpha-adrenoceptor antagonists or atypical antidepressants, such as nomifensine or bupropion.

Adrenergic alpha-Antagonists↗
PubMed1980

Differential effects of imipramine in rats as a function of DRL schedule value.

Imipramine, a tricyclic anti-depressant, has selective effects on differential-reinforcement-of-low-response-rate (DRL) schedule performance as a function of schedule value. On a DRL 9-sec schedule of water reinforcement, imipramine at doses of 2.5 to 20.0 mg/kg resulted in no significant change in the number of reinforcements or responses. A dose of 5.0 mg/kg imipramine, given to rats performing on a DRL > 72-sec schedule, produced a significant increase in the number of reinforcements and a concomittant decrease in responses. This effect was associated with a shift in the inter-response time (IRT) distribution to longer IRTs. Higher doses (20.0 and 40.0 mg/kg) decreased both response rate and reinforcement rate on the DRL 72-sec schedule. These findings demonstrate the importance of schedule parameters in determining the behavioral effects of imipramine.

Animals↗
PubMed1983

Discriminative stimulus control with imipramine: transfer to other anti-depressants.

Discriminative stimulus control with the tricyclic anti-depressant imipramine was attempted in three groups of rats; two of which were subjected to artificially stressful conditions. Only the unstressed group were shown capable of discriminating between the stimulus properties of intraperitoneal 10 mg/kg imipramine and saline in a two-lever, food-motivated operant task. Discriminative performance with decreasing doses of imipramine was shown to be dose-responsive. The ability to discriminate the interoceptive cue produced by imipramine was observed to transfer to a 10 mg/kg dose of both amitriptyline and desmethylimipramine. The results suggest a common tricyclic anti-depressant cueing property.

Amitriptyline↗
PubMed1987

Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals.

The present study was aimed at investigating in rats whether a common mechanism might underlie the reversal of depressive-like behaviors by classical antidepressants and by GABA agonists such as muscimol. Blockade of GABA transmission with picrotoxin (1 mg/kg IP) abolished the muscimol (0.5-1 mg/kg)-induced reduction of immobility in the swimming test and the reversal of escape failures in the learned helplessness paradigm. Conversely, picrotoxin was found not to reduce the efficacy of imipramine-like drugs in these same animal models. The combination of muscimol and tricyclics given at subeffective doses resulted in behavioral changes that can be accounted for by an additive interaction between these two classes of drugs. These data confirm the antidepressant-like profile of GABA agonists but suggest that it is unlikely that the primary antidepressant mechanism of conventional antidepressants involves GABA-A receptors. In the swimming test, prazosin (2 mg/kg), an alpha adrenoceptor blocker, antagonized the reduction of immobility produced by both muscimol and imipramine-like drugs. In the learned helplessness paradigm, penbutolol (0.25-0.5 mg/kg) and, though to a lesser extent prazosin, counter-acted the reversal of escape failures caused by muscimol and imipramine. On the basis of these data, it is tempting to speculate that increased transmitter outflow at noradrenergic receptors may be an essential component in the mechanism of action of imipramine-like drugs but also of GABA agonists.

Animals↗
PubMed1988

The relative efficacy of buspirone, imipramine and placebo in panic disorder: a preliminary report.

There is a need for safe effective alternatives to benzodiazepines in the treatment of panic disorder. Buspirone, a new nonbenzodiazepine anxiolytic, is compared to imipramine and placebo in the treatment of panic disorder in an 8 week double-blind controlled study of 52 randomly assigned patients. Weekly assessments were made using the Hamilton Anxiety Scale, the Sheehan Clinician Rated Anxiety Scale, the Sheehan Patient Rated Anxiety Scale, the Phobia Scale, the Disability Scale, the Hamilton Depression Scale, the Montgomery Asberg Depression Scale, the Investigator Rated Global Improvement Scale and the Patient Rated Global Improvement Scale. Preliminary results of repeated measures Anovas are reported. Imipramine was superior to placebo on many of the outcome measures. Imipramine was superior to buspirone on the Patient Rated Global Improvement Scale and on the Investigator Rated Global Improvement Scale, but not on other measures. Although buspirone appeared to be more effective than placebo, differences were not statistically significant. Some buspirone patients did very well compared to others, suggesting a possible bimodal distribution of response. Patients on buspirone had fewer and less disruptive side effects than those on imipramine.

Adult↗
PubMed1988

Long-term imipramine treatment differentially affects fenfluramine-induced suppression of food intake and locomotor activity.

Administration of fenfluramine to rats produced decreases in one-hour food intake and locomotor activity. Short-term (2-6 days) or long-term (21-25 days) treatment with the tricyclic antidepressant, imipramine, did not affect daily food intake, body weight gain or baseline locomotor activity when compared to saline treatment. However, long-term but not short-term imipramine treatment attenuated fenfluramine-induced decreases in one-hour food intake. On the other hand, neither short-term nor long-term imipramine treatment affected fenfluramine-induced decreases in locomotor activity. These findings demonstrate a differential effect of long-term imipramine treatment on fenfluramine-induced suppression of food intake and locomotor activity.

Animals↗
PubMed1988

The interactive effects of cocaine and imipramine on self-stimulation train-duration thresholds.

The present experiment examined the ability of the tricyclic antidepressant imipramine to influence cocaine's effect on intracranial self-stimulation. Following a predrug, saline injection period, cocaine hydrochloride (10, 20 or 30 mg/kg) was injected (IP) in 19 rats implanted with ventral tegmental area electrodes. Cocaine treatment uniformly decreased self-stimulation train-duration thresholds. In the next phase, the subjects were divided into two groups. One group received cocaine (as in the previous phase) and the other received cocaine plus imipramine (10 mg/kg, IP). Imipramine doubled cocaine's effect on self-stimulation train-duration thresholds. In addition, several other effects of cocaine (e.g., bradycardia, rear-limb dyskinesia) were potentiated by imipramine treatment. The results suggest that care must be exercised when treating cocaine abuse with tricyclic antidepressants since coadministration of these drugs intensifies cocaine's effects.

Animals↗
PubMed1989

Long-term imipramine treatment potentiates m-chlorophenylpiperazine-induced changes in prolactin but not corticosterone or growth hormone levels in rats.

Intravenous administration of m-chlorophenylpiperazine (m-CPP, a selective 5-HT agonist) to rats produced increases in plasma prolactin and corticosterone and a decrease in plasma growth hormone concentrations. Long-term but not short-term imipramine treatment potentiated m-CPP's effect on plasma prolactin, but not its effects on corticosterone or growth hormone. Short-term or long-term imipramine treatment did not produce significant changes in baseline levels of prolactin, corticosterone or growth hormone. These findings are compatible with development of functional supersensitivity of 5-HT receptors mediating prolactin release. Lack of potentiation of m-CPP's effects on corticosterone and growth hormone following long-term imipramine treatment suggests either differential regulation of these hormones by serotonergic and possibly other mechanisms, or different 5-HT receptor subtypes mediating the release of these hormones. Alternatively, adaptive changes in other aminergic neurotransmitter mechanisms such as the noradrenergic system may account for the differential effect of long-term imipramine treatment on m-CPP-induced neuroendocrine changes.

Animals↗
PubMed1990

Effect of chronic variable stress on monoamine receptors: influence of imipramine administration.

Adult male rats were exposed to a series of unpredictable stressors, a paradigm considered to be a model of experimental depression, with or without concurrent administration of imipramine. One day after the last stress event of the chronic regime, binding of cortical beta-adrenoreceptors and the behavioral serotonin (5-HT) syndrome induced by 5-methoxy-N,N,dimethyltryptamine (5-MeODMT) were determined in all the experimental groups. Stressed rats showed an "up-regulation" of cortical beta-adrenergic sites, while similar values to control rats were observed when stressed animals were administered imipramine. Regarding the behavioral 5-HT syndrome, comparable behavioral scores were observed between controls and chronically stressed rats. The combination of chronic exposure to different stressors with imipramine treatment resulted in a significant increase of forepaw treading and Straub tail scores. The probable facilitation of behavioral deficits induced by this scheme of chronic stress and the recovery following concurrent administration of imipramine are discussed.

Animals↗
PubMed1991

Autoradiographic analysis of the in vivo distribution of 3H-imipramine and 3H-desipramine in brain: comparison to in vitro binding patterns.

Using high resolution autoradiographic techniques, the distribution of radioactivity in forebrain and brainstem was assessed after IV injection of 3H-impramine or 3H-desipramine. Results were compared with regional binding of the drugs to brain sections in vitro. Similar topographic binding of 3H-imipramine and 3H-desipramine was observed in vitro among brain regions, except in the paraventricular nucleus of the hypothalamus and locus coeruleus, where binding was greater for 3H-desipramine. For both 3H-desipramine and 3H-imipramine, some brain regions that exhibited high binding in vitro also showed high accumulation after in vivo injection. However, certain regions that contained high densities of binding sites for the antidepressant drugs as measured by in vitro binding showed very low accumulation of radioactivity after in vivo treatment. Such regions included the dentate gyrus of the hippocampus, layer 1 of piriform cortex, caudate-putamen, pontine and midbrain central gray, and cerebellar granular layer. Compared to in vitro binding of the drugs, the distribution of imipramine and desipramine in vivo appears more anatomically selective. For imipramine, primary sites of action in vivo, as indicated by the topographic distribution in brain, appear to be the locus coeruleus, hippocampus, lateral septal nucleus, and amygdala. For desipramine, the greatest accumulation in vivo was found in the locus coeruleus, paraventricular nucleus of the hypothalamus, and anterior thalamic nuclei.

Animals↗
PubMed1991

The effect of imipramine and lithium on "learned helplessness" and acetylcholinesterase in rat brain.

The effect of short- and long-term treatment with imipramine and lithium on shock stress-induced escape failures in a shuttlebox (the "learned helplessness" model of depression) was investigated in rats. Acetylcholinesterase (AChE) activity was measured in the frontal cortex, hippocampus and striatum after the shuttlebox test. Imipramine was found to normalize escape behavior, whereas lithium further aggravated escape behavior. No correlation was found between escape behavior and AChE activity in the three brain areas investigated. However, a significant decrease in AChE activity in striatum was found in rats exposed either to shock stress and no drug treatment or to drug treatment and no shock stress. In rats exposed to the combination of shock stress and drug (imipramine or lithium), a slight or no decrease of AChE activity occurred. Exposure to shock stress alone produced no changes in AChE activity in the hippocampus and frontal cortex. In conclusion, lithium did not have an antidepressant effect on "learned helplessness" and AChE activity was not correlated to escape behavior. However, both imipramine and lithium normalized the decreased level of AChE activity in striatum in rats exposed to shock stress.

Acetylcholinesterase↗
PubMed1995

Ethological comparison of the effects of diazepam and acute/chronic imipramine on the behaviour of mice in the elevated plus-maze.

Recent clinical evidence suggests that the tricyclic antidepressant imipramine is effective against not only panic disorder but also generalized anxiety disorder. Although most animal models of anxiety appear to be insensitive to this agent, such work has almost invariably employed an acute treatment regimen. In the present study, ethological methods have been used to assess in detail the effects of acute and chronic imipramine treatment on the behaviour of male DBA/2 mice in the elevated plus-maze test. In contrast to acutely administered diazepam (1 mg/kg), which produced a significant anxiolytic profile on standard and ethological measures, neither acute nor chronic (daily, 15 days) treatment with imipramine (0-20 mg/kg) was associated with anxiety reduction. Data are discussed in relation to test sensitivity factors and the nonspecific mechanism of action of imipramine.

Animals↗
PubMed1981

Bromocriptine and imipramine in endogenous depression. A double-blind controlled trial in out-patients.

Among 33 out-patients with endogenous depression, 16 were treated with bromocriptine (10-60 mg/day, mean 34) and 17 with imipramine (75-250 mg/day, mean 143). The total score on the Hamilton Rating Scale decreased during 6-week treatment from 19.9 to 7.8 in the bromocriptine group (P less than 0.001) and from 20.1 to 6.1 in the imipramine group (P less than 0.001). There was no significant difference between the two groups. The main side-effects were for bromocriptine: nausea, dizziness, and headache; for imipramine; dryness of mouth, dizziness, and sweating. This study suggests an antidepressant effect of bromocriptine although, due to the possibility of Type II error, it may not necessarily be equal to that of imipramine.

Adolescent↗
PubMed1983

A double blind comparison of the efficacy and safety of trazodone and imipramine in endogenous depression.

In a 6-week double blind non-crossover study, trazodone and imipramine have been compared in the treatment of patients with severe endogenous depression. By random allocation, 13 patients entered each treatment group. The mean maintenance dosage of trazodone was 300 mg (range 200-350 mg) and of imipramine 160 mg (range 150-175 mg). Some evidence is presented to suggest that trazodone may have an earlier anxiolytic effect than imipramine by day 4 and a greater antidepressant effect by day 22 of treatment. Apart from the frequency of impaired visual accommodation being significantly greater in the imipramine group, there were no differences between the treatments with respect to side-effects. No abnormalities were found from laboratory investigations and ECG assessments.

Adult↗
PubMedDate not supplied

Alprazolam versus imipramine in depressed out-patients with neurovegetative signs.

The purpose of this study was to compare the safety and efficacy of a relatively new antidepressant drug, alprazolam (a triazolobenzodiazepine) with imipramine in the treatment of 60 depressed symptomatic volunteers. Eligible patients were randomly assigned after a 1-week washout to one of the medications and followed for 6 treatment weeks. Contrary to the earlier report of Feighner et al. (1983), who found alprazolam superior to imipramine and placebo, but consistent with Rush et al. (1985) we find imipramine superior in efficacy to alprazolam on a variety of symptoms. Both the present study and Rush's study employed patients with signs indicative of response to tricyclics. Feighner's patients may have been the type who tend to be less responsive to tricyclics but may be more responsive to alprazolam. Some of our data also show that alprazolam may have a more advantageous effect in the early weeks of treatment but is overtaken in subsequent treatment weeks by imipramine.

Adolescent↗