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At least 955 records · Page 53Linked to original sources
PubMed1990

Selective adenylate cyclase increase in the limbic area of long-term imipramine-treated rats.

Long-term administration of imipramine to rats produced an increase in the Vmax of forskolin- or guanylylimidodiphosphate (Gpp(NH))p-activated adenylate cyclase only in the limbic area. This effect was prevented by the daily administration of alpha-methyl-p-tyrosine (alpha-MPT), given together with imipramine, at a dose (50 mg/kg) which had no effect on adenylate cyclase activity per se. The time course of the effects of chronic imipramine on dopaminergic transmission in the limbic area showed that the decrease in both D-1 receptor number and adenylate cyclase stimulation by dopamine (DA) reached significance on day 8 of treatment and were maximal on day 15. The Vmax of the enzyme started to increase on day 15 and was further increased on day 21. Possible mechanisms underlying these effects are discussed.

Adenylyl Cyclases↗
PubMed1991

Repeated treatment with imipramine potentiates cocaine-induced dopamine release and motor stimulation.

The stimulatory effect of cocaine on locomotor activity and on dopamine efflux from the ventral striatum was studied in rats chronically treated with the antidepressant imipramine. Chronic imipramine (20 mg/kg per day for 3 weeks) potentiated by about 2-fold cocaine-stimulated motor activity and extracellular dopamine concentrations. The results indicate that chronic imipramine facilitates mesolimbic dopamine neurotransmission by potentiating the mechanism which is thought to mediate the rewarding effects of cocaine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Neural adaptation in response to chronic imipramine and electroconvulsive shock: evidence for separate mechanisms.

The effects of chronic imipramine and electroconvulsive shock alone or combined were assessed on rat brain beta-adrenoceptors and serotonin2 (5-HT2) receptors and on dynorphin and thyrotropin releasing hormone (TRH) levels. These treatments resulted in regionally discrete and treatment-specific patterns of change in beta-adrenoceptor and 5-HT2 receptor density and in TRH and dynorphin levels. Electroconvulsive shock eliminated the serotonergic component of hippocampal DHA binding, suggesting an effect of this treatment on 5-HT1 receptors. The effects of combined electroconvulsive shock and imipramine treatments on cortical 5-HT2 and beta-adrenoceptor density appeared to be the additive sum of the individual treatment effects. No treatment interaction was observed on hippocampal 5-HT2 and beta-adrenoceptors, except after day 2. No treatment interaction on peptide content was observed at any time. These results demonstrate independent anatomical specificity for the effects of electroconvulsive shock and imipramine and provide evidence that the mechanisms responsible for their antidepressant actions differ.

Animals↗
PubMed1994

Reversal by imipramine of beta-adrenoceptor up-regulation induced in a chronic mild stress model of depression.

Male Wistar rats were subjected to a chronic mild stress procedure involving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly intervals. After the first 3 weeks, when stressed animals displayed a reduction of sucrose consumption, the control and stressed groups were divided into subgroups receiving daily placebo or imipramine (10 mg/kg/day) treatment. After 5 weeks of treatment, 24 h after the last injection, the rats were killed and beta-adrenoceptor density and affinity in cortical membrane preparations and the accumulation of cyclic AMP in cortical slices stimulated with noradrenaline were assessed. While in stressed placebo-treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually returned to control values. The stressed placebo-treated rats also displayed an increase in cortical beta-adrenoceptor density (by 34%) with no changes in affinity, and an increase (22%) in the cyclic AMP response to noradrenaline in cortical slices. Imipramine, which in non-stressed rats did not affect sucrose intake but depressed the beta-adrenoceptor density and the cyclic AMP response, reversed the stress-induced decrease in sucrose consumption and the increase in the beta-adrenoceptor density; at physiological noradrenaline concentrations it also reduced the enhanced cyclic AMP response. The results suggest that the chronic mild stress procedure produces behavioral and biochemical changes consistent with a realistic model of depression in animals.

Adenylyl Cyclases↗
PubMed1992

Abnormal platelet 5-hydroxytryptamine uptake and imipramine binding in postnatal dysphoria.

Platelet 14C-5-hydroxytryptamine (14C-5-HT) uptake, 3H-imipramine binding and monoamine oxidase (MAO) activity were measured in women 5 days postpartum and compared with depression scores (Edinburgh Postnatal Depression Scale) at that time and 6 weeks later. Mean Km of 14C-5-HT uptake was significantly reduced in the group showing dysphoria at 5 days (p less than 0.01). Mean Kd of 3H-imipramine binding was significantly increased in the group who later went on to become depressed at 6 weeks postpartum (p less than 0.03). Vmax for 14C-5-HT uptake, Bmax for 3H-imipramine binding and MAO activity did not differ between depressed and non-depressed patients on either occasion. Although the observed changes manifested in a system known to be disturbed in other forms of depression, they were in affinity rather than Bmax or Vmax. Even though probably not of direct physiological significance, such results, if confirmed, together with other pointers in the literature, suggest biochemical abnormalities specific to the puerperal period.

Adult↗
PubMedDate not supplied

Effect of fluvoxamine, imipramine and placebo on catecholamine function in depressed outpatients.

Many of the specific serotonin reuptake inhibitors appear to have some effect on noradrenergic function. Fluvoxamine is one of the newer agents and its specificity has not been fully assessed. Depressed patients participating in a study comparing the efficacy of fluvoxamine with imipramine and placebo collected 24 hour urine samples (N = 38) and had plasma samples drawn (N = 38) prior to and after 6 weeks of double blind treatment. Urine samples were analyzed for 24 hour output of MHPG, VMA, NMN, MN and HVA. Plasma samples were analyzed for NE levels. Imipramine treatment produced a reduction in urinary MHPG, an increase in the ratio of NMN to MHPG plus VMA, and a trend towards an increase in plasma NE which was significantly different than the effects seen in the fluvoxamine and placebo groups. There was an additional finding in the imipramine group of a significant correlation between percentage change in plasma NE and clinical improvement. Fluvoxamine treatment, on the other hand, produced no clear effect on any measure of noradrenergic function and the antidepressant efficacy of fluvoxamine was unrelated to any noradrenergic variable. These findings lend support to the hypothesis that fluvoxamine does not have significant effects on noradrenergic function.

Adolescent↗
PubMed1992

Imipramine induced lipidosis and dexamethasone effect: morphological and biochemical study in normal and chronic GM2 gangliosidosis fibroblasts.

A large heterogeneous group of lysosomotropic compounds with a common cationic amphiphilic structure induces in vitro and in vivo lysosomal lipid storage. The biochemical mechanism underlying the lipidosis is still the subject of investigation. The authors report the experimental effect of imipramine and dexamethasone on lysosomal system in cultured skin fibroblasts. Morphological and ultrastructural observations of cells treated with imipramine showed vacuoles with lipidic storage, enlarged lysosomes with electron translucent zones and normal appearance of all the other cytoplasmic organelles. The lysosomal enzyme activities were decreased on biochemical study. On the contrary, an increased enzyme activity was detected in the culture medium. Pretreatment with dexamethasone partially prevented the effect of imipramine. Our results suggest that tricyclic antidepressants may induce lysosomal lipidosis through a dysfunction in the recycling of mannose-6-phosphate receptors and in the trafficking of newly synthesized lysosomal enzymes. Moreover the data presented may provide a clue in understanding some of the side effects observed in patients chronically treated with antidepressant drugs.

Cells, Cultured↗
PubMed1984

Reduction of serotonin-2 receptors in rat cerebral cortex after subchronic administration of imipramine, chlorpromazine, and the combination thereof.

Combined administration of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of psychotic depression. The effects of subchronic administration of imipramine, chlorpromazine, or the combination, on serotonin 2 (5-HT2) receptors labeled by 3H-spiroperidol in rat cerebral cortex were studied to determine whether this synergism might be related to an effect on these receptors, which have been linked to the therapeutic action of antidepressants. Treatment with imipramine or chlorpromazine alone for 14 days decreased the density of 5-HT2 receptor binding sites in rat cortex; the combination of the two drugs produced a greater reduction in 5-HT2 binding sites than imipramine or chlorpromazine alone. Thus, the clinical synergism of this combination may be related, in part to the more extensive decrease in 5-HT2 binding sites it produces. The ability of chlorpromazine alone to decrease 5-HT2 binding sites might be relevant to reports that it has an independent antidepressant action.

Animals↗
PubMed1984

Reduced Vmax of 3H-serotonin uptake but unchanged 3H-imipramine binding in the platelets of untreated hypertensive subjects.

The uptake of 3H-serotonin, endogenous serotonin content and 3H-imipramine binding were measured in platelets of subjects with essential hypertension and matched control volunteers. The uptake of 3H-serotonin and endogenous serotonin levels in platelets were significantly reduced while 3H-imipramine binding did not differ in the two experimental groups. These results provide further evidence that the uptake site for serotonin and the binding site for 3H-imipramine although associated, may be modified independently.

Biological Transport↗
PubMed1985

Platelet 3H-imipramine binding distinguishes depression from Alzheimer dementia.

Platelet 3H-imipramine binding and serotonin uptake were studied simultaneously in normal subjects and in depressed, parkinsonian and Alzheimer's disease patients to investigate the usefulness of these variables in the diagnosis of depression in the elderly. Whereas Vmax of platelet serotonin uptake was significantly reduced in all patient groups compared to age matched normal subjects, the density of 3H-imipramine binding was reduced in depressed patients only. The lower Bmax values in depressed patients was independent of patient age. These data suggest that platelet 3H-imipramine binding may be a useful laboratory index which discriminates depression from dementia in the elderly.

Age Factors↗
PubMed1989

The asymmetry of 3H-imipramine binding may predict psychiatric illness.

The Bmax and Kd values for 3H-imipramine binding were measured in post-mortem human brains from drug-free selected psychiatric subject homicide victims (n = 15) and normal controls (n = 15). The two groups were comparable in age and gender. The number of imipramine binding sites (Bmax) in the frontal cortices of psychiatric subjects had significantly higher Bmax values in the left hemisphere than in the right hemisphere. Inversely, the number of imipramine binding sites (Bmax) in the frontal cortices of normal controls were significantly higher in the right brain than in the left brain. It was postulated that the inhibiting effect of central serotonin (5-HT) has weakened in psychiatric cases, therefore the change of presynaptic serotonergic activity might be associated with psychiatric illness in the left hemisphere of human brain.

Adolescent↗
PubMed1993

Aging and 3H-paroxetine binding in rat brain: effect of imipramine and tetrahydroacridine.

3H-Paroxetine (PA) binding was studied in the frontal cortex (FC) and hippocampus (H) of 4 mos (young), 15 mos (adult) and 24 mos (aged) old Fischer 344 rats. Bmax (maximum number of binding sites) of PA binding was significantly higher in the H of adult rats compared with either young or old rats. There was no difference in Bmax between young and old rats. No change in Kd was observed in H and Kd or Bmax in FC with age. We also studied the effect of imipramine and tetrahydroacridine (THA) on PA binding in FC and H. Both drugs inhibited PA binding in FC and H but THA was 2000 times less potent than imipramine. There was no effect of age on IC50 values of imipramine and THA. These observations suggest that the number of 5-HT transporter sites in the hippocampus increases with brain maturity but then drops significantly during old age. This finding may have implications for age-related decrements in learning and memory, thought to be mediated by hippocampal structures.

Aging↗
PubMed1996

Chronic imipramine treatment induces downregulation of alpha-2 receptors in rat's locus coeruleus and A2 region of the tractus solitarius.

Imipramine is an effective antidepressant agent that blocks the reuptake of monoamines. In order to understand some of its basic mechanisms of action, we investigated the effects of chronic imipramine administration (10 mg/kg, i.p.; 21 days) on the alpha-2 receptor population of several brain sites. Alpha-2 receptor density was estimated by in vitro autoradiography using [3H]Idazoxan. The densitometric analysis revealed a decreased receptor density in the A2 region of the tractus solitarius (20%) and locus coeruleus (16%). No changes were observed in the amygdala, pyriform cortex, periacueductal gray and the bed nucleus of the stria terminalis. These results suggest that chronic imipramine treatment selectively modulates the alpha-2 receptor population localized in the brain stem norepinephrine-rich nuclei and not in the population present on limbic structures innervated by noradrenergic terminal projections. The possible physiological consequences of this selective modulation of alpha-2 receptors are discussed.

Adrenergic alpha-Antagonists↗
PubMed1992

The effects of electroconvulsive shock or imipramine on subtypes of alpha 1-adrenoceptors in the frontal cortex of the rat.

The effects of repeated treatment (14 days) with electroconvulsive shock (ECS) or imipramine on binding sites on alpha 1-adrenoceptors in the rat were studied. The binding of [3H]prazosin studied with WB4101 and phentolamine, as binding inhibitors, showed the existence of two subtypes of alpha 1-adrenoceptor (alpha 1A and alpha 1B). Proportions of the alpha 1A and alpha 1B binding sites were about 3:7 in the frontal cortex and 9:1 in the hippocampus. Pretreatment of the membranes with chlorethylclonidine (CEC) almost abolished the alpha 1B binding sites. Inhibition of the binding of [3H]prazosin studied with antidepressants (imipramine, desipramine, maprotiline and mianserin) showed that these drugs bound to alpha 1-adrenoceptors with low affinity, in an apparent monophasic manner. The characteristics of the alpha 1A and alpha 1B binding sites were studied by the binding assay with [3H]prazosin, in the presence of a small concentration (2 nM) of WB4101 to mask the alpha 1A binding sites, as well as the assay without WB4101, for the total alpha 1-adrenoceptor (alpha 1A and alpha 1B) binding. Repeated treatment with electroconvulsive shock increased but that with imipramine decreased, the density of the alpha 1B binding sites in the frontal cortex, without change of the affinity. Neither treatment affected the alpha 1A binding sites in the frontal cortex. The alpha 1-adrenoceptors (alpha 1A and alpha 1B) in the hippocampus were not affected at all by these repeated treatments. The electroconvulsive shock-induced increase in the alpha 1B binding sites in the frontal cortex of the rat could contribute to differences in clinical effects between electroconvulsive shock and antidepressant drugs.

Adrenergic alpha-Antagonists↗
PubMed1990

Chronic administration of imipramine antagonizes deranged circadian rhythm phases in individually housed rats.

The circadian rhythms of hypothalamic serotonin (5HT), tryptophan (TP) and 5-hydroxy-indoleacetic acid (5HIAA), and serum corticosterone were determined in male Wistar rats. The animals underwent a five-week 12:12-hr light/dark cycle conditioning period and were divided into three groups: rats housed four to a cage (group C, control), rats housed individually (group I), and rats housed individually and treated for two weeks with 10 mg/kg/day of imipramine continuously administered by osmotic pumps implanted under the skin (group T). Significant differences were found in the acrophases of 5HT, TP and 5HIAA between group I and group C, and corticosterone mesor was higher in group I than in group C. On the contrary, no differences were observed between group T (individually housed, but given imipramine) and group C. Therefore, chronically administered imipramine antagonizes the circadian changes induced by individual housing.

Animals↗
PubMed1990

Behavioral effects of chronic imipramine treatment in genetically nervous pointer dogs.

The genetically nervous pointer dog has been proposed as a model for human anxiety disorders. In a double-blind placebo-controlled study, seventeen nervous pointer dogs were treated for four weeks with imipramine hydrochloride (10 mg/kg), a potent antipanic agent in humans. Although three of the dogs demonstrated marked improvement to imipramine but not placebo treatment after short-term administration, chronic imipramine failed to modify the aberrant behavior in any of the dogs. These findings are discussed in the context of the nervous pointer dog as a model for human anxiety disorders.

Animals↗
PubMed1975

Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs.

Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra. This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control. Imipramine had no anticholinergic effect on the bladder and the urethra. It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system. No change was noticed in the intravesical or arterial pressures.

Adrenergic alpha-Agonists↗
PubMed1978

Comparative in vitro effects of imipramine, oxybutynin, and flavoxate on rabbit detrusor.

The ability of imipramine, oxybutynin, and flavoxate to antagonize carbamylcholine and barium chloride (BaCl2)-induced contractions of rabbit detrusor, and to block impulse conduction in desheathed frog sciatic nerves has been assessed in vitro. Impiramine exerts noncompetitive carbamylcholine and BaCl2 blockade by 10(-5) M and a local anesthetic effect equipotent with that of tetracaine. Oxybutynin exerts a strong competitive antagonism of carbamylcholine by 10(-8) M, a noncompetitive antagonism of BaCl2 equivalent to that of imipramine, and moderate local anesthetic activity. Flavoxate, under these experimental conditions exerts little anticholinergic, antispasmodis, or local anesthetic activity. Imipramine and oxybutynin thus demonstrate a number of smooth muscle effects by which their therapeutic actions may be exerted. The mechanisms of action of flavoxate remain obscure.

Anesthetics, Local↗