Effects of chlorpromazine and imipramine on rat heart subcellular membranes

Dhalla, Naranjan S.; Lee, Sheu L.; Takeo, Satoshi; Panagia, Vincenzo; Bhayana, Veena

doi:10.1016/0006-2952(80)90387-1

Cited by 19 publications

(7 citation statements)

References 28 publications

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“…Control assays did not contain the drugs in the incubation medium. The concentration of the drugs used in the present investigation was chosen on the basis of previous studies using imipramine in vitro (12) and the solubility of fluoxetine in the buffer.…”

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confidence: 99%

In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

Zanatta

Nascimento

Barros

et al. 2001

Braz J Med Biol Res

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The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na + ,K + -ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na + ,K + -ATPase activity. There was a significant decrease (10%) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27%) in Na + ,K + -ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na + ,K + -ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na + ,K + -ATPase activity is decreased in bipolar patients.

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confidence: 99%

In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

Zanatta

Nascimento

Barros

et al. 2001

Braz J Med Biol Res

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“…The possibility that DMI per se exerts a direct effect on the enzyme was ruled out because the presence of DMI in vitro caused inhibition rather than stimulation, when assayed both on Na 1 ,K 1 -ATPase activity and on ouabain binding. The inhibition of ATPase by DMI has been attributed to a destabilizing effect of the drug on cell membranes (Dhalla et al, 1980). In vitro DMI inhibited 3 H-ouabain binding with a IC 50 circa 10 24 M, a concentration within the range capable of inhibiting Na 1 ,K 1 -ATPase activity (Gilbert et al, 1978, Dhalla et al, 1980, Carfagna et al, 1993.…”

Section: Discussionmentioning

confidence: 98%

“…The inhibition of ATPase by DMI has been attributed to a destabilizing effect of the drug on cell membranes (Dhalla et al, 1980). In vitro DMI inhibited 3 H-ouabain binding with a IC 50 circa 10 24 M, a concentration within the range capable of inhibiting Na 1 ,K 1 -ATPase activity (Gilbert et al, 1978, Dhalla et al, 1980, Carfagna et al, 1993. Such a concentration is too high to be considered as pharmacological and specific and is actually higher than the concentration attained after the administration of an acute dose of DMI.…”

Section: Discussionmentioning

confidence: 98%

Desipramine modulates3H-ouabain binding in rat hypothalamus

et al. 1997

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“…Dhalla et al (4) reported that imipramine decreased calcium binding of the sarcolemmal fraction in subcellular membranes of the rat heart. Thus, it was suggested that the direct depressant properties of this compound were related to changes in the mobilization of intracellular calcium.…”

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confidence: 99%

“…These experiments show that imi pramine produces a fairly uniform suppression of the tension development at all examined frequencies, whereas verapamil produces a greater depression of the developed tension at higher frequency rates. Dhalla et al (4) reported that imipramine inhibited sarcolemmal Ca" binding activity, and such a decrease in Ca" binding caused by this agent may be the result of a reduction in sarcolemmal Ca" stores available for release upon depolarization of the myo cardium.…”

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confidence: 99%