Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IMIPRAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1994

The effect of chronic imipramine administration on the densities of 5-HT1A and 5-HT2 receptors and the abundances of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat.

We have recently demonstrated that the LEW/N rat contains lower concentrations of cortical and hippocampal 5-HT1A receptors compared with the F344/N and out-bred HSD rats. To further characterize these strains, we investigated the effect of chronic (8 wk) imipramine administration (5 mg/kg/day) on 5-HT1A and 5-HT2 receptor densities and mRNA in the cortex and hippocampus and 5-HT transporter mRNA in the dorsal raphe of LEW/N, HSD, and F344/N rats, using quantitative autoradiography and in situ hybridization histochemistry. After imipramine treatment, a significant increase in the levels of hippocampal 5-HT1A receptors, but not mRNA, was observed in LEW/N rats while the abundance of hippocampal 5-HT1A receptor mRNA, but not 5-HT1A receptor densities, decreased in F344/N rats. Cortical and hippocampal 5-HT2 receptor densities, but not mRNA, significantly decreased after imipramine administration in all three strains. Finally, 5-HT1A receptor densities and the abundance of mRNAs encoding the 5-HT1A receptor and 5-HT transporter in the dorsal raphe remained unaltered after imipramine administration in all three strains. The effects of imipramine on the levels of cortical and hippocampal 5-HT1A and 5-HT2 receptors and their transcripts, therefore, appear to be strain-dependent. The implications of these findings are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Partial characterization of solubilized platelet imipramine binding sites using a new probe, [3H]3-cyanoimipramine ([3H]Ro 11-2465).

Evidence suggests that [3H]imipramine labels the recognition site of the neuronal 5-hydroxytryptamine uptake mechanism. We are investigating the linkage between these binding sites and the carrier by biochemical characterization. [3H]Imipramine-labelled sites have been solubilized from outdated human platelets using the detergent digitonin. [3H]3-Cyanoimipramine binds persistently to these sites in the presence of Na+ at 4 degrees C. At higher temperatures, and in the absence of Na+, this ligand acts reversibly. We report the use of this pseudo-irreversible ligand in the initial molecular characterization of the recognition molecule. To confirm that this ligand occupies the [3H]imipramine-labelled sites, human platelets were prelabelled with 3-cyanoimipramine before incubating with [3H]imipramine. Only low affinity [3H]imipramine binding remained. The majority of the 3-cyanoimipramine was irreversibly bound under these conditions as shown by the use of the 3H compound. Gel permeation chromatography of [3H]3-cyanoimipramine-prelabelled platelet membranes solubilized with digitonin indicated a Stokes' radius of 6.3 nm. This is larger than values previously determined for cholate-solubilized sites. We conclude that [3H]3-cyanoimipramine will be useful for further purification and reconstitution studies.

Binding, Competitive↗
PubMed1986

The effect of imipramine treatment on brain serotonin receptors and beta-adrenoceptors and on pineal beta-adrenergic function in adult and aged rats.

The effect of age and of imipramine treatment on cortical serotonin and beta-adrenergic binding sites and on pineal N-acetylserotonin and melatonin were examined in Fischer-344 rats. Cortical serotonin-1 and -2 receptor binding was reduced by 15 and 22.5% respectively, in 24 vs. 6 months old animals. Ten single daily imipramine (10 mg/kg) injections in the aged animals resulted in reductions in both types of serotonin sites, while in adult animals significant binding reduction occurred only at the 5HT2 site. Cortical beta-adrenoceptor binding was also diminished in the aged rats. Imipramine treatment elicited a significantly greater decrease in these adrenergic sites in the aged (39.2%) than in the adult (27.6%) animals. In the pineal gland, N-acetylserotonin and melatonin content were reduced by age; imipramine treatment induced decreases in both indoles in the adult animals and a reduction in N-acetylserotonin in the aged animals. These age-related effects of imipramine on cortical serotonin receptor and beta-adrenoceptor binding and on pineal indoles may be a consequence of the higher drug and metabolite (desmethylimipramine) blood and tissue concentrations which were found in the aged animals.

Aging↗
PubMed1993

Triiodothyronine increases desipramine with changing the concentrations of monoamines, in the brain of rat given imipramine.

After treatment with triiodothyronine (T3) for 5 days, rats received a single i.p. injection of imipramine. The concentrations of imipramine and desipramine decreased and increased, respectively, in the brains of T3-treated rats, and the elimination half-time of desipramine was increased. In rats that had received imipramine for 7 days, cotreatment with T3 also resulted in reduced imipramine and elevated desipramine concentrations in the brain. Coadministration of T3 with imipramine appeared to accelerate the desipramine-induced changes in norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations in brain. Since T3 treatment elevated the 5-hydroxyindole acetic acid concentration in the brain, the concentration in rats receiving both drugs was equivalent to that of vehicle-treated rats.

Animals↗
PubMed1988

[3H]imipramine binding in the retinas of chickens and pigs.

High-affinity [3H]imipramine binding sites detected in the brain are associated with the neural uptake mechanism for serotonin. In this study [3H]imipramine binding in the retinal synaptosomal P2-fraction, which contains the serotonin-accumulating nerve terminals, was characterized using two different animal species, chicken and pig, and with a wide range of imipramine concentrations. The specific binding of imipramine was saturable. When homogenates were prepared from fresh retinas, a high-affinity binding site in the nanomolar range and a low-affinity binding site in the micromolar range were always found. In the pig retina only a high-affinity binding site was found after freezing. The Bmax-value of the high-affinity binding was about 10 times greater in the retinas of pigs than in those of chickens; Bmax-values for fresh homogenates were 1711- and 235 fmol mg-1 protein and those for frozen homogenates were 2066- and 146 fmol mg-1 protein in pig and chicken retinas, respectively. Our results confirm the complexity of imipramine binding described for different regions of the brain. The great difference in the Bmax-values of the high-affinity binding in chicken and pig retinas might indicate differences between species in the serotonergic system.

Animals↗
PubMed1990

Hypoaminoacidemia caused by imipramine but not by clenbuterol is dissociable from hyperglycemia and hyperinsulinemia.

The effects of the tricyclic antidepressant imipramine (20 mg/kg) and the beta-adrenoceptor agonist clenbuterol (0.5 mg/kg) on the serum concentrations of tyrosine, tryptophan, glucose and insulin were compared 30 min after intraperitoneal injection. The drugs had nearly identical effects on serum tyrosine, which was reduced to 73% of control by both drugs, and on tryptophan, which was reduced to 72% by imipramine and to 66% by clenbuterol. In contrast, whereas clenbuterol raised serum glucose to 174% and insulin to 379% of control, imipramine had no significant effects on either glucose or insulin. The results clearly demonstrate that the effects of imipramine on blood amino acid levels are dissociable from effects on glucose and insulin. We conclude, therefore, that hypoaminoacidemia caused by imipramine is not mediated by stimulating insulin release.

Animals↗
PubMed1983

Lack of association between [3H]imipramine binding sites and uptake of serotonin in control, depressed and schizophrenic patients.

Uptake of serotonin and [3H]imipramine binding were studied in parallel in the platelets of control, depressed and schizophrenic patients. In the depressed patient group, uptake of serotonin was consistently reduced while [3H]imipramine binding was only decreased in a number of these patients. In the schizophrenic group, uptake of serotonin was reduced to 62% of control with no changes in [3H]imipramine binding being observed. These data demonstrate a clear dissociation between uptake of serotonin and [3H]imipramine binding sites in human platelets. The possible functional role of these [3H]imipramine binding sites remains to be determined.

Blood Platelets↗
PubMed1983

[3H]-imipramine binding sites in fawn-hooded rats.

The existence of high-affinity [3H]-imipramine recognition sites was demonstrated in membranes prepared from the cerebral cortex, hypothalamus and platelets obtained from fawn-hooded rats. The Bmax and Kd values for [3H]-imipramine binding to cerebral cortical membranes were virtually identical to those obtained with cortical membrane preparations of Sprague-Dawley rats. An NBR strain of rats, genetically related to fawn-hooded rats, was found to have significantly higher levels of [3H]-imipramine binding sites in cerebral cortical membranes when compared to fawn-hooded and Sprague-Dawley rats. All four strains of rats examined possessed extremely high densities of [3H]-imipramine binding sites in a purified platelet membrane fraction. These results do not support the finding of others that the cerebral cortex and platelets of fawn-hooded rats are virtually devoid of [3H]-imipramine binding sites.

Animals↗
PubMed1985

Changes induced by corticosterone and adrenalectomy in synaptosomal and platelet uptake and binding of 5-HT. The relationship to [3H]imipramine binding.

A comparative study of the effect of adrenalectomy, treatment with corticosterone, and imipramine on platelet an synaptosomal uptake was undertaken. One day after adrenalectomy, uptake of 5-hydroxytryptamine (5-HT) in the platelet and the hypothalamus was significantly decreased with an increase in the apparent Km, but the uptake of 5-HT of the cerebral synaptosomes was unchanged. In this group, the Kd of low affinity binding of 5-HT was also increased in the hypothalamic synaptosomes and in the platelet preparations. Treatment with corticosterone (5 mg/kg, i.m.) restored the decrease in the uptake of 5-HT induced by adrenalectomy in the hypothalamic synaptosomes and in the platelets, and significantly increased the uptake of 5-HT of these fractions in sham-operated rats. The binding of 5-HT was unchanged by acute treatment with corticosterone. The effectiveness of imipramine varied with the preparation and treatment group. The IC50 of the cerebral synaptosomal preparation was greater than that of the hypothalamic synaptosomal preparation. Using this latter preparation, the IC50 for imipramine in adrenalectomised, sham-operated and corticosterone-treated rats were found to be 0.04, 0.09 and 0.25 microM, respectively. These changes in sensitivity to imipramine were not reflected in the binding of [3H]imipramine which was unchanged.

Adrenalectomy↗
PubMed1987

Effects of subchronic treatment with imipramine, zimelidine and alaproclate on regional tissue levels of substance P- and neurokinin A/neurokinin B-like immunoreactivity in the brain and spinal cord of the rat.

The effects of subchronic (14 day) treatment with the inhibitors at the uptake of monoamines, zimelidine, alaproclate and imipramine, on regional levels of substance P (SP) and other tachykinins in tissue in the central nervous system of the rat were studied by radioimmunoassay. In the ventral spinal cord, in which substance P is known to exist together with 5-hydroxytryptamine (5-HT), in the terminals of descending neurones, treatment with the selective inhibitors of the uptake of 5-HT zimelidine (2 X 10 mumol/kg p.o.) or alaproclate (2 X 10 mumol/kg or 2 X 20 mumol/kg p.o.), increased the level of substance P-like immunoreactivity (SP-LI). The effect of alaproclate appeared to be dose-dependent. After treatment with imipramine (2 X 10 mumol/kg p.o.) only a tendency to increased levels of substance P-like immunoreactivity spinal cord was seen. Treatment with alaproclate, at the highest dose level, also elevated the concentration of neurokinin A/neurokinin B-like immunoreactivity (NKA/NKB-LI) in the ventral spinal cord. In the frontal cortex, in which separate monoaminergic and tachykinin-containing neurones interact, treatment with imipramine reduced the levels of SP-LI and NKA/NKB-LI, while treatment with alaproclate had the opposite effect. In the periaqueductal grey matter, treatment with zimelidine and alaproclate increased the levels of SP-LI and NKA/NKB-LI, while treatment with imipramine increased only the level of NKA/NKB-LI. In conclusion, subchronic treatment of rats with inhibitors of the uptake of monoamines induced changes in levels of tachykinin in frontal cortex, periaqueductal grey and spinal cord. The selective inhibitors of the uptake zimelidine and alaproclate, had similar effects on levels of tachykinin, while the inhibitor of the uptake of 5-HT and noradrenaline, imipramine induced changes in the frontal cortex, which were qualitatively different from the effects of zimelidine and alaproclate. Furthermore, the levels of different tachykinins were not always changed in parallel by the same treatment.

Alanine↗
PubMed1994

Effects of acute and chronic administration of the antidepressants, imipramine, phenelzine and mianserin, on the social behaviour of mice.

Effects of imipramine, phenelzine and mianserin on the behaviour of male CDl mice were examined after a single intraperitoneal injection (imipramine, 15.8 and 63.2 mumol/kg; phenelzine, 1 and 8 mumol/kg); mianserin, 0.12 and 0.48 mumol/kg) and after administration for 12-16 days in the drinking fluid (mean daily intake; imipramine, 15.8 and 63.2 mumol/kg; phenelzine, 1 and 8 mumol/kg; mianserin, 0.12, 0.48 and 1.92 mumol/kg). Behaviour was examined by ethological procedures during 5 min encounters with an untreated partner in a familiar situation, the animal's home cage, and in the more aversive environment of an unfamiliar cage. At 30 min after injection, the higher doses of acutely administered imipramine and mianserin decreased aggressive behaviour in the unfamiliar cage. In the home cage, effects of mianserin were only slight, whereas imipramine reduced social investigation at the larger dose and in both test environments decreased digging. Phenelzine increased social investigation in both environments. After chronic administration, each of the drugs increased social investigation in the neutral cage and home cage at some of the dose levels, indicating potential anxiolytic efficacy. Mianserin showed the additional effect of enhancing digging during tests in the neutral cage, which may correlate with its anxiolytic actions. Phenelzine was the only antidepressant to increase aggression during encounters in the neutral cage after chronic administration. The significance of these findings is discussed.

Aggression↗
PubMed1985

Serotonin uptake and imipramine binding in rat platelets after chronic dexamethasone and amitriptyline treatment.

Chronic adrenocorticotrophin treatment was shown to decrease platelet 5HT uptake, increase Km and decrease Vmax. Similarly, chronic dexamethasone treatment decreased 5HT uptake, but had no effect on the Kd and Bmax of high affinity imipramine binding sites in the platelets. Chronic amitriptyline treatment induced similar changes, with the exception that the drug induced a decrease in the number of high affinity imipramine binding sites. Chronic dexamethasone treatment potentiated the effects of amitriptyline and decreased the IC50 of imipramine and desipramine as 5HT uptake inhibitors in vitro. The results suggest that whereas 5HT uptake is related to high affinity imipramine binding sites, it can be modified independently of the high affinity imipramine binding.

Adrenocorticotropic Hormone↗
PubMed1993

Effects of imipramine on circadian rhythms in the golden hamster.

The effects of the antidepressant imipramine on circadian organization were studied in wild-type and tau-mutant golden hamsters. Chronic imipramine treatment in doses ranging from 0-50 mg kg-1.day-1 depressed general activity and body temperature and caused a reduction in body weight but had no significant effect on circadian organization. Imipramine treatment did not affect the rate of reentrainment after a 6-h advance in the light-dark cycle, did not alter the advanced-phase angle of entrainment of tau-mutant hamsters, did not affect the free-running period of wild type hamsters, and did not alter the phase-response curve to light pulses. Because imipramine, a clinically effective antidepressant, did not have any measurable effect on the circadian system in these experiments, our results do not provide support for the hypothesis that the antidepressant action of imipramine is mediated by alterations in the circadian system.

Animals↗
PubMed1981

Relevance of tryptophan and tyrosine availability in endogenous and 'non-endogenous' depressives treated with imipramine or clomipramine.

This study was performed on 65 depressed in-patients who were included in previously reported trials of imipramine and clomipramine. Before and during treatment, blood samples were collected for estimation of the availability of tryptophan and tyrosine by measurement of their plasma ratios to competing amino acids, and for determination of plasma steady-state concentrations of imipramine, clomipramine and their demethylated metabolites. The patients were classified as endogenous or 'non-endogenous' depressives by means of diagnostic rating scales, and therapeutic efficacy was evaluated by means of the Hamilton rating scales. Neither imipramine nor clomipramine increased the availability of tryptophan or tyrosine. Three biochemical regions were defined: a low region including mostly patients with subnormal availability of both tryptophan and tyrosine, a medium region, and a high region including mostly patients with supernormal precursor availabilities. Endogenous depressives showed about the same biochemical distribution as controls whereas there tended to be a proportionately higher number of 'non-endogenous' depressives within the low region. Patients in the low region, irrespective of diagnostic classification, improved faster and more on imipramine than patients in the medium and high regions with comparable plasma drug levels. Patients on clomipramine tended to show a relationship between precursor availabilities and clinical response but no definite conclusion could be drawn from these data. The results suggest that determination of the pre-treatment tryptophan and tyrosine availability may be superior to diagnostic classification in predicting response to imipramine. The possible mode of action of tricyclic antidepressants is briefly discussed.

Biological Availability↗
PubMed1984

3H-imipramine binding sites in brain down-regulated by chronic nortriptyline and haloperidol but not mianserin treatment.

Specific binding of 3H-imipramine to membrane preparations from the cerebral cortex and hippocampus was measured in rats given nortriptyline (10 mg/kg/day), mianserin (10 mg/kg/day), haloperidol (1 mg/kg/day), or saline for 21 days and killed 48 hours after the last injection. Chronic treatment with nortriptyline resulted in a significant decrease in density (Bmax) of 3H-imipramine binding sites in the hippocampus but not in cerebral cortex without significant changes in binding affinity (Kd). Mianserin treatment failed to alter Bmax and Kd of specific 3H-imipramine binding in either of the two brain regions. Repeated administration of haloperidol also produced a lowering in the number of 3H-imipramine binding sites (Bmax) in the hippocampus. The results indicate that the ability of tricyclic antidepressants to down-regulate 3H-imipramine recognition sites in the brain is not shared by nontricylic antidepressants such as mianserin. The observation that down-regulation of binding can also be produced by a typical antipsychotic drug, haloperidol, suggests that this phenomenon may not be related to the mode of therapeutic effect of antidepressants.

Animals↗
PubMed1983

Desmethylimipramine and imipramine on left ventricular function and the ECG: a randomized crossover design.

Sixteen severely depressed patients participated in a double-blind randomized, crossover study to compare the effects of desmethylimipramine and imipramine on left ventricular function and the electrocardiogram. Following a drug-free week, patients had 3 weeks of therapy each with desmethylimipramine and imipramine. During each treatment period systolic time intervals, echocardiograms and high-fidelity electrocardiograms were recorded. There was no difference between desmethylimipramine and imipramine on (1) systolic time intervals, (2) shortening fraction or mean velocity of circumferential shortening, or (3) the electrocardiogram. There was a difference between the drug-free period and desmethylimipramine or imipramine on the PEPc (P less than 0.05) and the PEP/LVET ratio (P less than 0.05); on the R-R (P less than 0.05), PR (P less than 0.05), QRS (P less than 0.05), and QTc (P less than 0.05) intervals; but no difference on the LVETc or shortening fraction or the mean velocity of circumferential shortening. Drugs such as desmethylimipramine and imipramine which prolong intraventricular conduction can probably be expected to prolong the PEP and PEP/LVET. For this reason systolic time intervals have limitations in assessing myocardial function and the echocardiogram more reliably estimates myocardial performance in patients receiving tricyclic antidepressants.

Adult↗
PubMedDate not supplied

3H-imipramine binding in aged mouse brain: regulation by ions and serotonin.

The density of binding sites (Bmax) for 3H-imipramine was elevated in cerebral cortical, hypothalamic and hippocampal membranes from 24 month old male C57BL/6J mice. Cerebellar binding was constant with increasing age. There were no changes in the equilibrium dissociation constant (Kd) for 3H-imipramine in any brain region. The increase in the binding of 3H-imipramine induced by sodium and chloride ions in vitro was diminished in cerebral cortical homogenates from aged mice; both the sodium-sensitive and chloride-sensitive components of binding were about 50% less in aged mice. Dose-response curves indicated that the effectiveness with which chloride enhanced binding was similar with age, even though the absolute increase in binding was less. The rate of dissociation of 3H-imipramine from cerebral cortical homogenates was similar with age and serotonin slowed the rate of dissociation equally at all ages. Possible mechanisms for the age-related increase in brain 3H-imipramine binding are discussed. Ion-sensitive binding is discussed in relationship to the current controversy surrounding desipramine-sensitive versus ion-sensitive binding.

Aging↗
PubMed1978

Acute cardiovascular toxicity of trazodone, etoperidone and imipramine in rats.

The cardiovascular effects of trazodone, a broad-spectrum antidepressant and its analogue etoperidone, were compared with imipramine, following intravenous infusion in rats. Their effects on electrocardiogram and blood pressure were simultaneously recorded until cardiac arrest. Hypotension was the primary effect of trazodone and etoperidone. ECG changes, i.e. lengthening of the PR interval, were observed only when the blood pressure reached very low values. On the other hand, imipramine produced first the well known ECG changes and then a drop in blood pressure. As far as mortality was concerned, trazodone was the least toxic drug, followed by etoperidone, whereas imipramine was most toxic; these differences being in agreement with the LD50 values reported in rats by the i.v. route. It is concluded that trazodone and etoperidone produce in rats cardiovascular effects, which are different from those of imipramine. Moreover these differences are consistent with their pharmacological properties, particularly their interaction with catecholamines, which are inhibited by trazodone or etoperidone and potentiated by imipramine.

Animals↗