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 1,657 records · Page 92Linked to original sources
PubMed1982

A quantitative study in the rat on the relationship between imipramine levels in brain and serum.

Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg-1 to 15 mumol kg-1, 350 ng--5 mg kg-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or gamma-hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2 x 36 mumol kg-1 (10 mg kg-1), last dose 89 mumol kg-1 (25 mg kg-1), 2--3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.

Animals↗
PubMed1985

Ro 11-2465 (cyan-imipramine), citalopram and their N-desmethyl metabolites: effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities.

Ro 11-2465 (cianopramine, cyan-imipramine) and citalopram (CIT), putative antidepressant drugs, are very potent and selective 5-hydroxytryptamine (5-HT) uptake inhibitors in vitro. This study investigated the effects of these drugs and their desmethyl metabolites, Ro 12-5419 (desmethylcianopramine, cyan-desipramine) and desmethylcitalopram (DCIT), respectively, on the uptake of 5-HT and noradrenaline (NA) in vivo [protection against H 77/77 (4, alpha-dimethyl-metatyramine)-induced displacement of 5-HT and NA] and on related pharmacological activities. All the investigated drugs antagonized H 77/77-induced displacement of 5-HT in the rat brain, though the effects of the metabolites were considerably weaker than those of the parent compounds. The H 77/77-induced displacement of brain NA in rats and mice was antagonized only by Ro 12-5419 and Ro 11-2465. All the drugs potentiated the pressor response to 5-HT in pithed rats; however, Ro 12-5419 and particularly Ro 11-2465 could also block the response when used in higher doses (greater than or equal to 0.1 mg/kg). Only Ro 12-5419 and Ro 11-2465 were able to potentiate the pressor response to NA. Ro 12-5419 also potentiated thyrotropin releasing hormone (TRH) hyperthermia and antagonized reserpine hypothermia in mice; Ro 11-2465 potentiated the TRH hyperthermia only. CIT and DCIT were inactive in both these tests. Of all the four drugs only CIT and Ro 12-5419 considerably stimulated the hind limb flexor reflex in spinal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

A comparison of plasma and serum levels of two tricyclic antidepressants: imipramine and desipramine.

This study was performed to determine the difference, if any, between serum and plasma levels of the tricyclic antidepressant drugs imipramine and desipramine. Serum and plasma samples were drawn simultaneously from patients taking either of these drugs. Statistical analysis indicated no difference in the drug levels; that is, serum and plasma levels were identical.

Blood Chemical Analysis↗
PubMed1983

Effects of a single oral dose of 3-cyano-imipramine on serotonin uptake and content of platelets in healthy volunteers.

Changes in platelet serotonin uptake and content were investigated following administration of a single oral dose of 3-cyano-imipramine to healthy volunteers. The uptake of 3H-serotonin by platelets harvested from these subjects was almost completely inhibited 4 h after dose administration. This inhibition continued for at least 24 h. Plasma taken from the subjects inhibited the uptake of 3H-serotonin by platelets isolated from non-treated subjects. A small but significant reduction in platelet serotonin content was observed 3.75 h after dosing and was still evident after 24 h.

Administration, Oral↗
PubMed1982

Effects of chlordiazepoxide and imipramine on maze patrolling within two different maze configurations by psychogenetically selected lines of rats.

Male rats of two lines of rats psychogenetically selected and bred for extremes in performance in shuttle box avoidance received an acute IP injection of chlordiazepoxide (CDP; 2.5, 5.0, 10.0 mg/kg), imipramine HCl (IMI: 0.33, 1.0, or 3.0 mg/kg), or vehicle. The rats were placed, 35 min after injection, in an enclosed maze with either a simple configuration with an unilluminated central arena or a complex configuration with a brightly illuminated central arena, and spontaneous maze patrolling was evaluated. Total locomotor activity during the 6-min maze test was significantly reduced by 5--10 mg/kg CDP for both RHA/Verh and RLA/Verh lines of rats in both the simple and the complex maze configurations. Treatment with 10 mg/kg CDP reduced the total explored area for both rat lines in both maze configurations. In addition, the maze area explored by RHA/Verh rats was also reduced by 5.0 mg/kg CDP for the simple configuration and by 2.5 and 5.0 mg/kg CDP for the complex configuration. Entry into the unilluminated central field of the simple maze was reduced by 5--10 mg/kg CDP only in RHA/Verh rats. In contrast, 2.5 mg/kg CDP significantly increased entry into the brightly illuminated central arena of the complex maze for the RLA/Verh rats. The doses of IMI used were without effect on the parameters of maze patrolling behavior evaluated, with the single exception that the locomotor activity of RHA/Verh rats tested in the simple maze configuration was decreased by 3.0 mg/kg IMI. The results indicate that, although the effects of CDP were generally similar for total activity and the area explored in the two psychogenetic lines investigated, there was a qualitative difference in its effect on entry into an illuminated arena.

Animals↗
PubMed1977

[Memorization and central catecholamines after a craniocervical injury carried out in rats: influence of imipramine administration (author's transl)].

A craniocervical injury has been carried out in rats (with head free to move) so that they get through a whiplash without any coma. Two days after the whiplash, comparable with a postcommotional syndrome, the acquisition of a labyrinth behavior is disturbed and, 7 days later, the retention is still disturbed. This disturbance of retention is not observed when the acquisition is performed before the whiplash. These data agree with the clinical observations, and we hypothesize a possible causal relation between the disturbance of learning behavior and the decrease of noradrenaline cerebral level induced by the whiplash. Treatment with imipramine (1 mg/kg) after the whiplash is able to remove these behavioral and biochemical disturbances.

Animals↗
PubMed1981

Cerebral pharmacokinetics of imipramine in rats after single and multiple dosages.

Pharmacokinetics of imipramine (IMI) and its active metabolite, desipramine (DMI) was studied in rats after administration of a single dose of 10 mg/kg IMI, or after chronic administration of this dose once or twice a day for 14 days. The elimination curves of IMI and DMI from the blood and brain show that both the whole body and the brain behave as multi-compartment systems. Maximum concentrations of IMI and DMI in blood and brain appear at the same time, indicating rapid metabolism of IMI: the concentrations were significantly higher in the brain than in the blood. After the chronic treatment the maximum blood and cerebral levels of IMI and DMI were not much higher than after a single dose, but the elimination was slowed down. Brain concentration of IMI and DMI and brain IMI/DMI concentration ratio do not parallel those in the blood. After a prolonged treatment, once or twice a day, desipramine in the brain is present for the whole period between injections at concentrations sufficient to inhibit the noradrenaline uptake. If the drug is given twice a day, in addition to DMI also IMI is present for the whole time at concentration which may inhibit also serotonin uptake.

Animals↗
PubMed1983

Chronic treatment with imipramine: further functional evidence for the enhanced noradrenergic transmission in flexor reflex activity.

The chronic administration of imipramine (IMI; 10 mg/kg orally, twice daily for 14 days) enhanced the flexor reflex of the hind limb in the spinal rat. This effect was maintained for at least 72 h after termination of drug administration. Phenoxybenzamine but not cyproheptadine abolished the enhanced activity of the flexor reflex. After chronic administration of IMI high levels of desipramine (DMI) were found in the spinal cord, whereas IMI was not detectable there. No correlation was found between the levels of DMI in the spinal cord and the enhancement of the flexor reflex amplitude. A single i.v. dose of DMI facilitated the flexor reflex for a short period of time. In rats treated chronically with IMI, the binding of 3H-prazosin, a ligand of alpha 1-adrenoceptors, to spinal cord tissue was increased. The present results are a further argument for the previously advanced hypothesis that chronic administration of antidepressant drugs leads to an enhanced noradrenergic transmission, probably by increasing the number of alpha 1-adrenoceptors.

Animals↗
PubMed1986

Differential effects of cimetidine and ranitidine on imipramine demethylation and desmethylimipramine hydroxylation by human liver microsomes.

The effect of cimetidine and ranitidine on the demethylation of imipramine (IMI) and on the hydroxylation of desmethylimipramine (DMI) was studied in microsomes from four human livers. Cimetidine inhibited both demethylation of IMI and 2-hydroxylation of DMI, whilst the effect of ranitidine was not statistically significant. 2-hydroxylation of DMI is probably mediated by debrisoquine hydroxylase, a cytochrome P-450 isozyme that is monogenically controlled. The results suggest that cimetidine inhibits this enzyme.

Cimetidine↗
PubMed1976

Comparison of single dose kinetics of imipramine, nortriptyline and antipyrine in man.

The single dose kinetics of imipramine (IP), nortriptyline (NT), and antipyrine (AP) were compared in 7 healthy subjects. Test doses of AP were given intravenously and test doses of IP and NT were given both orally and by intravenous infusion. The plasma concentration/time curves after intravenous IP and NT were analysed according to a 2-compartment open model. In addition a blood flow independent 'true' clearance was calculated according to a sinusoidal perfusion model. Indirect estimates of hepatic blood flow were obtained from the oral and i.v. plasma concentration/time curves after NT administration. Compared to NT, IP had statistically significant higher clearances, shorter half-lives, and smaller apparent volumes of distribution. There was a significant correlation between apparent volume of distribution (Vdbeta) of IP and NT (n = 5, r = 0.85), but only a weak correlation between the clearance measurements of the two compounds. Systemic clearance of AP and IP showed some positive correlation (n = 7, r = 0.73), whereas there were no significant correlations between AP and NT kinetics. The data indicate that inter- and intraindividual variations in hepatic blood flow may influence the measurements. Other possible sources of variability are individual differences in hepatic extraction kinetics, and differences in binding to blood constituents.

Administration, Oral↗
PubMed1989

Decreased gamma-aminobutyric acid (GABA) modulatory effect on rat vas deferens neurotransmission after chronic administration of imipramine.

1. Chronic (10 mg/kg, i.p., once daily for 14 days) but not acute (10 mg/kg, i.p., 24 hr) administration of imipramine resulted in a decrease in both the responsiveness and the sensitivity of the contractions of the isolated rat vas deferens elicited by field stimulation to GABA and (-)-baclofen. 2. In contrast, clonidine and isoproterenol effects were not altered by either treatment. 3. This study shows for the first time that GABA action in the peripheral nervous system is altered by chronic treatment with antidepressants, possibly by inducing changes in a postreceptor element.

Animals↗
PubMed1979

Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: increasing the power of bioavailability tests.

A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.

Adolescent↗
PubMed1988

Adrenergic, serotoninergic, histaminergic, and imipramine binding sites in post-mortal human cerebral microvessel preparations.

Cerebral microvessels were prepared from fresh and frozen human brain samples obtained from autopsy cases. Structural integrity and purity of the microvessels were confirmed by light and electron microscopy, and by measurement of the enzymatic marker gamma-glutamyltranspeptidase. Similar morphological and enzymatic characteristics were found for the microvessels prepared from fresh and frozen brain samples. Radioligand binding experiments indicated the presence both in the "fresh" and "frozen" microvessel preparations of specific alpha 1-, alpha 2-, and beta-adrenergic, histamine H1, serotonin S1 and imipramine binding sites, although the density of beta-adrenergic and histamine H1 specific binding sites were lower in the frozen samples than in the fresh samples. Low levels of specific binding to muscarinic, GABAergic and serotonin S2 sites (with respect to the specific binding densities in the crude homogenates) were found in the microvessel preparations.

Adult↗
PubMed1982

Different pharmacokinetic and pharmacological effects following acute and chronic treatment with imipramine.

Two schedules of imipramine (IM) administration were compared, a single intraperitoneal dose (10 mg/kg) (I) and chronic oral dosage (10 mg/kg twice a day for 14 days) (II). During schedule I, IMI reached maximal concentration in brain twice as high as that of its metabolite, desipramine (DMI), but disappeared more rapidly. During schedule II, DMI achieved concentrations twice as high as those of IMI which were maintained in a long-lasting plateau and there were considerable differences in areas of brain concentration curves. During schedule I, depletion of brain noradrenaline (NA) induced by H77/77 and of 5-hydroxytryptamine (5-HT) by p-chloro-amphetamine, were inhibited. During schedule II, after DMI concentration had become high and that of IMI low, only NA depletion but not that of 5-HT, was inhibited. At the same time, fenfluramine-induced hyperthermia was not antagonized although it was inhibited in schedule I. These findings may be relevant to those obtained clinically and may help to shed light on mechanisms of antidepressant action.

Animals↗
PubMed1995

The effect of prolonged treatment with imipramine and electroconvulsive shock on the levels of endogenous enkephalins in the nucleus accumbens and the ventral tegmentum of the rat.

The present study was designed to find out whether the prolonged administration of imipramine (IMI) or electroconvulsive shock (ECS) influences levels of endogenous enkephalins in the nucleus accumbens (NAS) and the ventral tegmentum (VTA) of the rat. Ressults indicate that treatment with IMI as well as with ECS has a profound effect on the levels of enkephalins in both structures. In the NAS both treatments lead to an increase in the levels of endogenous enkephalins and this effect is accompanied by an increase in mRNA coding for proenkephalin (measured by in situ hybridization) in this structure, indicating the enhancement of biosynthesis of endogenous enkephalinergic peptides following antidepressant treatment. The results are discussed in the light of the hypothesis concerning the influence of endogenous enkephalins on mesolimbic dopamine neurons, the activity of which plays a crucial role in the etiology of depression.

Animals↗
PubMed1991

Platelet imipramine binding in intensive care unit suicidal patients.

3H-Imipramine binding in relation to serotonergic function was studied in patients hospitalized following a suicide attempt. Comparison with a control group showed a highly significant difference in Bmax values. The results suggest, at least a posteriori, a biological alteration as the basis of suicidal behaviour. Although it is impossible to attribute a suicidal attempt to the alteration or to a predisposing pre-existent condition, this biological marker may be useful in evaluating suicidal risk and also short- and long-term prognosis.

Adult↗