Cerebral pharmacokinetics of imipramine in rats after single and multiple dosages

Daniel, W.A.; Adamus, Anna; Melzacka, M; Szymura, Joanna; Vetulani, Jerzy

doi:10.1007/bf00503818

Cited by 64 publications

(16 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of this observation resides in the fact that the daily administration of imipramine to rats results in steady state levels of desipramine being achieved before day 4 (Nagy, 1977). Moreover, the chronic adminis-tration of imipramine is not associated with a gradual accumulation of desimipramine in rat brain (Daniel et al, 1981). These observations clearly argue against a receptor blocking effect and strongly support the concept of receptor subsensitivity.…”

Section: Discussionmentioning

confidence: 78%

Some effects of chronic antidepressant treatments on rat brain monoaminergic systems

1983

J. Neural Transmission

View full text Add to dashboard Cite

A range of established and putative antidepressant therapies were studied for the effect of their long-term administration on two facets of presynaptic monoaminergic functioning in rat brain, namely NE, DA, and 5-HT turnover and alpha 2-adrenoceptor sensitivity. Unless stated otherwise drugs (10 mg/kg) were injected i.p. twice daily for 14 days. ECT (100 mA for 1 s) was applied once daily for 10 days. Changes in turnover were indirectly assessed by measuring levels of metabolites. Brain levels of MHPG-SO4 were unchanged by chronic amitriptyline, imipramine, nisoxetine (20 mg/kg), nortriptyline, salbutamol (5 mg/kg), and ECT. Amitriptyline elicited a slight, but significant, increase in brain DOPAC content. Brain levels of 5-HIAA were increased by amitriptyline, imipramine, salbutamol, and ECT. An overall view of the results indicates that no common pattern of change was elicited by the range of antidepressant therapies studied. Central alpha 2-adrenoceptor sensitivity was assessed by investigating the effect of various therapies on the ability of clonidine (25 mg/kg i.p.) to decrease rat brain MHPG-SO4 content. The clonidine-induced fall was attenuated by desipramine, imipramine, and ECT. Amitriptyline, iprindole, mianserin, nisoxetine, nortriptyline, Org 6582 (10 mg/kg once daily), pargyline (25 mg/kg once daily), salbutamol, and trazodone were ineffective. The following chronic antidepressant therapies were investigated for their effect on rat frontal cortex 3H-clonidine binding: amitriptyline, desipramine, imipramine, iprindole, mianserin, nisoxetine, nortriptyline, pargyline, salbutamol, and ECT. CHronic, but not acute, pargyline decreased 3H-clonidine binding and this was due to a diminished number of binding sites. The induction of subsensitive presynaptic alpha 2-adrenoceptors in rat brain is not a property common to all forms of antidepressant therapies. Hence it cannot be the fundamental mode of action of antidepressants. No correlation exists between the changes in rat cortical 3H-clonidine binding and the observed changes in the sensitivity of central presynaptic alpha 2-adrenoceptors.

show abstract

Section: Discussionmentioning

confidence: 78%

Some effects of chronic antidepressant treatments on rat brain monoaminergic systems

1983

J. Neural Transmission

View full text Add to dashboard Cite

show abstract

“…(Paumier et al, 2015) and IMI (10 mg/kg, i.p.) (Daniel et al, 1981) for 35 consecutive days dissolved in physiological saline, respectively. Groups V -VII received 11 subcutaneous injections of rotenone (1.5 mg/kg) (Abdelkader et al, 2014) every other day starting from the 15 th day dissolved in DMSO.…”

Section: Experimental Designmentioning

confidence: 99%

Imipramine and amitriptyline ameliorate the rotenone model of Parkinson’s disease in rats

et al. 2016

View full text Add to dashboard Cite

“…imipramine and desipramine) also present short intracerebral half-lives, 46,47) must be emphasized that when given once or twice a day for 14 d they are present in the brain for the whole interval between injections at concentrations sufficient to inhibit noradrenaline and serotonin uptake. 48) In contrast, the lowest dose (3 mg/kg) induced a significant, but transient, increase in total caloric intake. This result was observed in the 16th to 18th day of CMI treatment, an effect that was neither macronutrient-specific nor followed by body weight gain (Table 2).…”

Section: Discussionmentioning

confidence: 93%

Effect of Chronic Treatment with Clomipramine on Food Intake, Macronutrient Selection and Body Weight Gain in Rats

Calegari

Gorenstein

Gentil

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Weight gain is a frequent side effect observed during drug treatment of psychiatric disorders.1) It often contributes towards patient non-compliance and discontinuation of the pharmacological treatment.2) Weight gain may also contribute to comorbidities such as hypertension, coronary heart disease, diabetes, and stroke. 3,4) Weight gain is also a relatively common problem during both acute and long-term treatment with antidepressants. It appears that tricyclic antidepressants (TCA) may be more likely to cause weight gain as compared to selective serotonin reuptake inhibitors (SSRIs), a class of antidepressant widely used in clinical practice. 5,6) Among them amitriptiline, doxepin, imipramine, trimipramine, maprotiline, nortriptyline, and clomipramine are reported to cause marked weight gain. 2)TCA may affect appetite by blocking the reuptake of serotonin and noradrenaline. Serotonin is recognized to have an influence on food intake and macronutrient selection. 7,8) Noradrenaline has also been shown to have an effect on food intake that opposes the effects of serotonin, but its effects on macronutrient selection are not clear. 7,9,10) TCA may also affect appetite by blocking histaminergic (H1) pathways. 11)However, the mechanisms underlying the weight gain induced by antidepressants treatment have yet to be understood. In clinical studies, it has been found that antidepressant drugs alter nutrient selection, inducing in particular a preference for high-carbohydrate or sweet foods. [12][13][14] Early efforts to model these effects in rats have led to contradictory results. For example, it has been shown that acute systemic injections of clomipramine selectively enhance carbohydrate intake.15) On the other hand, it has been reported that food intake was initially and significantly decreased by desmethylimipramine treatment but this effect progressively returned towards pretreatment levels over the course of the drug administration (30 d).16) Such discrepancies may be related to brain monoamine receptor neuroadaptations following chronic treatment with antidepressants.17-21) Nobrega and Coscina 22) evaluated the effects of the chronic treatment with two other TCA, amitriptyline and desipramine on food selection. They showed that desipramine decreased food intake and body weight, while amitriptiline did not change food intake and body weight or slightly reduced them in comparison to vehicle-treated controls. However, strict macronutrient protocols (using separate sources of pure macronutrients) have rarely been tested in rats following the chronic treatment with TCA. Therefore, it remains unclear whether this class of antidepressants change macronutrient selection and weight gain in rats. Given that and there is only limited evidence on the effects of TCA on macronutrient selection especially over long periods of drug treatment, the present study was carried out to explore the effects of chronic treatment with clomipramine (CMI) on food intake, macronutrient selection and body weight in male rats allowed to self-sel...

show abstract

Cerebral pharmacokinetics of imipramine in rats after single and multiple dosages

Cited by 64 publications

References 11 publications

Some effects of chronic antidepressant treatments on rat brain monoaminergic systems

Some effects of chronic antidepressant treatments on rat brain monoaminergic systems

Imipramine and amitriptyline ameliorate the rotenone model of Parkinson’s disease in rats

Effect of Chronic Treatment with Clomipramine on Food Intake, Macronutrient Selection and Body Weight Gain in Rats

Contact Info

Product

Resources

About