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PubMed1978

Subcellular distribution of [14C]5-hydroxytryptamine in the blood platelets of rabbits: effects of imipramine and and haloperidol.

Long-term (10 days) administration of imipramine [20 mg/(kg X d)] to rabbits significantly increases the Km value (4.0 micron) of 5-hydroxytryptamine uptake in their platelets compared to those of saline- (0.7 micron) or haloperidol- (0.4 micron) treated rabbits. Administration of haloperidol inhibits the 5-hydroxytryptamine uptake non-competitively, and in vitro it had an ID50 value of 22 micron. Intravenous injections of [14C]5-hydroxytryptamine were given to the animals 1 h before blood collection. After isolation of platelets, their sonicates were subjected to 30-60% continuous sucrose gradient centrifugation. The subcellular distribution of [14C]5-hydroxytryptamine indicates that imipramine treatment, in contrast to the control and haloperidol treatment, led to a shift in the exogenous 5-hydroxytryptamine peak from within the granular zone (d 1.18) to the extragranular cytoplasm (d 1.15). Compared to control values, the imipramine treatment caused 63% inhibition in the platelet Na-K-ATPase activity.

Animals↗
PubMed1976

Effects of imipramine, nomifensine and d-amphetamine on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase.

The three dissimilar structural antidepressant drugs, imipramine, nomifensine and d-amphetamine, were compared for their effects on type B monoamine oxidase, cyclic AMP phosphodiesterase and dopamine-beta-hydroxylase. Three antidepressant drugs caused a dose-dependent inhibition on type B monoamine oxidase. Of the three drugs, imipramine had a most potent effect. Unlike d-amphetamine, both imipramine and nomifensine inhibited the cyclic AMP phosphodiesterase activity at concentrations more than 10(-4)M. No effect was observed below this concentration. All drugs seemed to have little or no effects on the partially purified dopamine-beta-hydroxylase activity. The weak inhibitory effects of nomifensine on these three enzymes may not be attributable to its antidepressant properties. Morphine had no effect on the three enzyme activities.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Treatment of panic disorder in older adults: a pilot study comparison of alprazolam, imipramine, and placebo.

OBJECTIVE: Several studies have documented that a variety of pharmacological compounds are quite effective in controlling acute symptomatology of panic disorder in the general population. However, there is a paucity of such studies in the management of panic disorder in older adults (ages 55 and above). The purpose of this study was to gather pilot data in older patients with panic disorder to begin to assess the efficacy of two commonly-used antipanic medications, imipramine and alprazolam. METHOD: Twenty-five (n = 25 (23 females; 2 males); 18 completers, 7 dropouts) older panic disorder (DSM-III-R) patients (age range = 55-73; mean = 61.24) were studied in an eight-week randomized, parallel-groups, double-blind, placebo-controlled, flexible dose design. Outcome was assessed weekly by global change ratings (Hamilton Anxiety and Depression Scales; Physicians' Global Impression ratings) and panic diaries. Because of small sample size, we present data descriptively. RESULTS: Subjects in active medication groups evidenced reductions in panic attacks and in level of overall anxiety and depression. Therapeutic dosages were approximately half those commonly used in younger panic disorder patients. CONCLUSION: Our data suggest the comparable efficacy of alprazolam and imipramine in the short-term treatment of older adults with panic disorder. There is clearly the need for a larger scale placebo-controlled study, preferably comparing imipramine and/or alprazolam with one of the SSRIs, to substantiate our findings.

Aged↗
PubMed1990

Lithium and imipramin effects on paw preference in cats.

The effect of lithium and imipramin on paw preference was studied in cats. Paw preference was assessed by the food-reaching test. It was found that lithium decreased, and imipramin increased the asymmetry of paw use. The lithium effect was antagonized by imipramin. It was concluded that paw preference may reflect a biochemical asymmetry in the brain. These effects of these psychoactive drugs may be of importance for the origin and treatment of affective disorders.

Animals↗
PubMed1994

Metabolism of lofepramine and imipramine in liver microsomes from rat and man.

1. The in vitro metabolism of lofepramine was studied in comparison with imipramine. Both compounds were hydroxylated and demethylated by a NADPH-generating system in rat and human liver microsomes. 2. Three metabolites were in common for the two drugs, namely desipramine (DMI), 2-hydroxydesipramine (2-OH-DMI) and didesmethylimipramine (DDMI). 3. Lofepramine was also metabolized to three unique tricyclic metabolites. Comparisons with authentic reference compounds suggested that two of these metabolites were 2-hydroxylofepramine and desmethyllofepramine. 4. The ratio between the concentrations of DDMI and DMI was higher for lofepramine than imipramine. This is probably due to DDMI formation via two parallel metabolic pathways of lofepramine, i.e. DMI and desmethyllofepramine, respectively. 5. It is speculated that the different metabolic pattern of lofepramine as compared with desipramine and imipramine is of importance for the therapeutic profile of the drug.

Aminopyrine N-Demethylase↗
PubMed1986

Effect of imipramine on the circadian rhythm of plasma melatonin in unipolar depression.

The authors took a series of 20 serum samples over a 24-hr period for measurement of melatonin in four men and six women with Major Depressive Disorder (DSM-III), at baseline (depressed) and after 4 weeks on imipramine (150-200 mg/day) after achieving clinical remission. After successful treatment with imipramine, 24-hr secretion and peak levels of melatonin were significantly higher than at baseline, with no difference in time of peak level. Testing after 2 weeks of treatment (four subjects), with only a partial or no clinical response, revealed no differences compared with baseline. The therapeutic efficacy of imipramine may be associated with an enhancement of noradrenergic activity.

Adult↗
PubMed1988

Tricyclic imipramine modification of the circadian rhythms of hypothalamic serotonin, its precursors and acid catabolite in individually housed rats.

Circadian rhythms of serotonin (5HT), its precursors tryptophan (TP) and 5-hydroxy-tryptophan (5HTP) and its acid catabolite 5-hydroxy-indoleacetic acid (5HIAA), were determined in the hypothalamus of control rats and rats which had been treated continuously with subcutaneous imipramine (10 mg/kg/day) for 2 weeks. Rats were individually housed and entrained to LD 12:12. Controls showed the 5HT and TP peaks in the light and dark periods respectively, as reported in the literature, but no inverted correlation (antiphase) between 5HT and 5HIAA rhythms. Imipramine significantly modified circadian rhythm characteristics: the 5HT acrophase was advanced, that of TP and 5HIAA was delayed. Imipramine also significantly increased hypothalamic 5HT and TP concentrations.

5-Hydroxytryptophan↗
PubMed1996

Chronic administration of imipramine and lithium changes the phase-angle relationship between the activity and core body temperature circadian rhythms in rats.

Evidence suggests that there is an association between the pathophysiology of depression and a disturbance of circadian rhythms. Accordingly, attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of chronic administration of two clinically effective antidepressant agents, imipramine and lithium, on several circadian rhythms in the rat. Activity, core body temperature, and drinking rhythms were assessed in constant darkness (DD) and light-dark (LD) conditions. In DD, lithium significantly lengthened the circadian period of the activity, temperature, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantly increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle. These results indicate that although both drugs produced different effects on the circadian period of individual rhythms, both caused a relative phase advance of the temperature rhythm as compared to the activity rhythm, and this effect may be related to the similarity in their antidepressant effects.

Animals↗
PubMed1986

Pre- and postsynaptic localization of 3H-imipramine binding sites: action of 5-7 dihydroxytryptamine and triton X-100 on subcellular fractions of rat brain.

In rats injected intraventricularly with 5-7 dihydroxytryptamine there was a considerable reduction of 5-hydroxytryptamine and 5-hydroxyindol acetic acid content in cerebral cortex and hippocampus. After cell fractionation of these structures, a 37% reduction of 3H-imipramine binding was observed in the crude mitochondrial fraction of the treated rats, that contains the synaptosomes. In purified synaptosomal membranes the reduction was about 20%. Dissolution of the presynaptic membrane with 0.1 and 0.2% Triton X-100 on the treated membranes further reduced 3H-imipramine binding respectively by 25% and 40%, values similar to those obtained on control synaptosomal membranes. These findings were further substantiated using saturation experiments for the high affinity site of 3H-imipramine. The results obtained are discussed in relation to the possible mechanism of action of antidepressant drugs at the synaptic region, and the possible postsynaptic effect is emphasized.

5,7-Dihydroxytryptamine↗
PubMed1977

Lipid hemodialysis versus charcoal hemoperfusion in imipramine poisoning.

Previous experimental results have demonstrated the possibility of eliminating imipramine (14 C-IP) by hemodialysis. A simultaneous uptake of the substance by the polyvinyl chloride extracorporeal blood lines could be shown. Based on these results the imipramine absorption capacity of the blood lines and of the artificial kidney (Hollow Fiber Artificial Kidney, HFAK, Model 4) were studied. Imipramine (IP) absorption capacity of a usual blood-line set (arterial and venous, surface area 86,000 mm) was estimated to be 43 mg, and that of the HFAK to be 207 mg. Charcoal hemoperfusion (300 gm of coated activated coconut charcoal) eliminated more than 90% of IP from the blood within 3 hr if the initial IP blood concentration was 2 mg/ml. In comparison, lipid hemodialysis using 20% soybean oil as dialysate eliminated 95% of IP from the blood when the initial IP blood concentration was 1 mg/ml and 98% when the initial IP blood concentration was 2 mg/ml. In vivo studies on the elimination of IP by lipid (10%) hemodialysis demonstrated a substantial removal of the substance. Within 2 hr of treatment, 12% of the administered dose (75% of the LD50) was eliminated.

Adsorption↗
PubMed1985

Dopamine and isoproterenol in imipramine intoxication in the dog.

Artificially ventilated anesthetized dogs were given imipramine 7.5 mg/kg/hr i.v. In the first group (n = 6) mechanical cardiac activity was no longer detectable after a cumulative dose of 20.0 +/- 6.6 mg/kg (mean +/- sd). When aortic flow had decreased to 75% of its initial value, in a second group (n = 5) of experiments dopamine 10 micrograms/kg/min and in a third group (n = 5) isoproterenol 1 microgram/kg/min were administered i.v.. The doses of dopamine and isoproterenol were doubled when aortic flow had again decreased to 75% and 100%, respectively, of the original values. Cardiac mechanical activity was not detectable after a cumulative dose of 43.8 +/- 13.3 in the dopamine and 42.5 +/- 8.0 mg imipramine/kg in the isoproterenol group. These values differed significantly from that in the reference group (both 0.01 greater than p greater than 0.001). In the first group plasma imipramine concentrations at the end of the experiments were 3.06 +/- 0.66, in the second 3.36 +/- 0.66 and in the third 3.32 +/- 1.10 mg/1. Desipramine concentrations were 0.078 +/- 0.06, 0.162 +/- 0.076 and 0.383 +/- 0.09 mg/1 respectively. Dopamine induced a hemodynamic profile of low output and high pressure and isoproterenol one of low pressure and high output. It is concluded that dopamine combined with isoproterenol might be effective in counteracting the cardiodepressant action of imipramine.

Animals↗
PubMed1998

Should anxiety and insomnia influence antidepressant selection: a randomized comparison of fluoxetine and imipramine.

BACKGROUND: The more sedating antidepressants are often recommended for patients presenting with anxiety or insomnia. We examine whether baseline anxiety or insomnia symptoms (1) show differential response to fluoxetine or imipramine or (2) predict differences between drugs in overall clinical response or likelihood of medication discontinuation. METHOD: 336 health maintenance organization primary care patients beginning antidepressant treatment for depression were randomly assigned to an initial prescription for fluoxetine or imipramine. All subsequent care (medication dosage, change, or discontinuation) was managed as usual by the primary care physician. The 17-item Hamilton Rating Scale for Depression (HAM-D) and the Hopkins Symptom Checklist (SCL) anxiety and depression subscales were administered prior to randomization and 1 month later. RESULTS: Rates of improvement in insomnia (HAM-D insomnia items), agitation (HAM-D agitation item), and anxiety (SCL anxiety subscale) were essentially identical in the two treatment groups. Baseline level of insomnia did not predict significant differences between randomization groups in improvement in overall HAM-D score (p = .44) or SCL depression subscale (p = .44). Similarly, baseline level of anxiety did not predict significant differences in improvement in HAM-D (p = .19) or SCL depression subscale (p = .31). Patients assigned to fluoxetine were significantly less likely to change or discontinue antidepressant medication during the first month, but this difference did not vary according to baseline level of insomnia (p = .68) or anxiety (p = .25). CONCLUSION: Among patients with moderate depression, baseline levels of insomnia or anxiety should not influence the choice of fluoxetine or imipramine as an initial antidepressant.

Adult↗
PubMed1998

The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine.

BACKGROUND: Previous research has suggested that depressed patients, and particularly chronically depressed patients, have significant impairments in many areas of their lives. While previous studies suggested that these "psychosocial" impairments improve following pharmacologic treatment, no large scale definitive study using multiple measures of psychosocial functioning has been reported. METHOD: We assessed multiple domains of psychosocial functioning using interviewer-rated and self-report measures within the context of a 12-week acute treatment trial of sertraline and imipramine for patients with chronic depression (double depression and chronic major depression). We also compared the psychosocial functioning data of this sample before and after treatment with normative data available from published community samples. RESULTS: Chronically depressed patients manifested severe impairments in psychosocial functioning at baseline. After treatment with sertraline or imipramine, psychosocial functioning improved significantly. Significant improvements appeared relatively early in treatment (week 4). Despite these highly significant improvements in functioning during acute treatment, the study sample as a whole did not achieve levels of psychosocial functioning comparable to a comparator nondepressed community sample. However, patients who reached full symptomatic response (remission) during acute treatment did have levels of psychosocial functioning in most areas at endpoint that approached or equaled those of community samples. CONCLUSION: These results indicate that successful antidepressant treatment with sertraline or imipramine can alleviate the severe psychosocial impairments found in chronic depression.

Adaptation, Psychological↗
PubMedDate not supplied

Interaction of chlorpromazine and imipramine with model membranes.

The aim of the present study is to examine the effect of phospholipids on the lipid destabilization induced by chlorpromazine (CPZ) and imipramine (IP) at different levels of pH. The large unilamellar vesicles (LUV) are formed in the presence of calcein (60 mM). The vesicles containing calcein have been incubated in the presence of CPZ and IP at pH 4.5 and pH 8. At pH 4.5 CPZ and IP induce a rapid release of the calcein encapsulated in the liposomes. Calcein release, at equal concentrations of pharmacological agent, is more important by CPZ than by IP. At pH 8, the calcein release was more important than at pH 4.5; this effect appears to be more significant for the CPZ than for the IP. In conclusion, the insertion of chlorpromazine and imipramine into large unilamellar vesicles is accompanied by a strong destabilization of the vesicles. These effects appear more significant for chlorpromazine than for imipramine.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

[Influence of imipramine on arousal from winter hibernation].

Imipramine (20 and 50 mg/kg intraperitoneally) is shown to delay the arousal of gophers from hibernation. This effect is similar to the action of serotonin (5 mg/kg) and 5-oxytryptophan (50 mg/kg). In the latter, however, the action on the thermogenesis is most pronounced and, because of this the warming up of the gophers is inhibited, while imipramine acts on the arousal. Tranylcypromine (20 mg/kg) failed to exert any substantial effect on the worming up and arousal of gophers from hibernation and attenuated the action of imipramine.

5-Hydroxytryptophan↗
PubMed1975

[Clinical trial of lofepramine versus imipramine].

Lofepramin is a new derivative of imipramine. Its effects and side effects were compared to those of imipramine in a double-blind trial. 49 hospitalized patients, suffering from endogenous depression, were treated for 20 days with 210 mg lofepramin daily and 52 other patients with 150 mg imipramine daily. The results of the repeated psychiatric examinations were documented using the AMP system. Both substances proved to have high antidepressant effects and showed no significant difference in the quality of their effects.

Acetophenones↗
PubMed2000

The role of dopamine D2 receptor in the behavioral effects of imipramine--study with the use of antisense oligonucleotides.

Antisense strategies have a potential to specifically block the production of a given protein, e.g. receptor subtype, thus may help to uncover its behavioral and/or biochemical function. In the present study we demonstrated the utility of this approach for studying the role of dopamine D2 receptors in the anti-immobility effect of imipramine in the forced swimming test. Following intracerebroventricular (i.c.v.) administration of phosphorothioate oligonucleotide complementary to mRNA encoding for dopamine D2 receptors (D2 antisense ODN; 1 nmol/1 microl H2O, twice a day for 5 days) to the rats, the decrease in the locomotor activity (shortened total distance travelled and decrease in vertical activity, without differences in the stereotypic movements of animals), as well as the decrease of specific binding of [3H]raclopride in the striatum and limbic forebrain were observed. At the same time, i.c.v. administration of D2 antisense ODN reversed the effect of imipramine in the forced swimming test, what may indicate that the dopamine D2 receptors play a significant role in the behavioral anti-immobility effects of imipramine.

Animals↗
PubMed1975

Imipramine-caused interference with levodopa absorption from the gastrointestinal tract in rats.

Rats treated for 3 or 30 days with imipramine (30 mg/kg) have impaired absorption of a single dose of 14C-levodopa. Treated animals retain larger amounts of radioactivity in their gastric lumen and this interfers with delivery of levodopa to intestinal absorptive sites. Tissues of treated animals have lower levels of radioactivity than controls and urinary excretion of radioactivity is also lessened. Imipramine does not interfere with uptake of levodopa by everted sacs of rat jejunum. Imipramine does, however, interfere with the transit of radioactivity through the gastrointestinal tract of rats, since treated animals have lower ileal radioactivity than controls. Lower relative concentration of levodopa metabolites in gastric fluid and tissue may reflect an interference of uptake of levodopa by gastric enterochromaffin-like cells.

Animals↗