Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Manzanares, Jorge; Tamargo, Juan

doi:10.1111/j.1476-5381.1983.tb10509.x

Cited by 15 publications

(14 citation statements)

References 22 publications

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“…Thus, the addition of therapeutic concentrations of amoxapine to the perfusate produced similar changes in untreated and pretreated atria. These results are in contrast to those obtained with imipramine (Manzanares & Tamargo, 1982) and could explain why adverse cardiovascular effects are rarely observed during chronic treatment of depressed patients with amoxapine (Smith & Ayd, 1981;Jue et al, 1982). One possible reason for the differences between imipramine and amoxapine could be related to the pharmacokinetics of these compounds.…”

Section: Discussionmentioning

confidence: 76%

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Electrophysiological effects of amoxapine in untreated and in amoxapine‐pretreated rat atria

Delgado

Manzanares

Tamargo

et al. 1986

British J Pharmacology

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1 The effects of amoxapine (10-_-10-4M) have been studied in rat atrial fibres obtained from untreated animals and animals pretreated for 28 days with amoxapine (1Omg kg-', i.p.). 2 In untreated atria amoxapine reduced atrial rate, contractile force and dfldt prolonged the sinus node recovery time and decreased atrial excitability.3 Amoxapine also decreased amplitude and V,.,, of the upstroke, prolonged the duration of the action potential (APD) and effective refractory period (ERP) and reduced the resting membrane potential. 4 During the treatment with amoxapine behavioural and cardiovascular adverse effects, including hypotension, tachycardia and prolongation of the Q-Tc, were observed. However, with the exception ofthe ERP which was significantly prolonged in pretreated atria, pretreatment with amoxapine did not modify the control values of the measured parameters compared to those obtained in untreated atria. 5 Further addition of amoxapine produced similar changes in both pretreated and untreated atria. However, in contrast to untreated atria, in pretreated atria the prolongation of the ERP produced by amoxapine exceeded the prolongation of the APD and thus, the ERP/APD ratio increased. The decrease in atrial excitability was also more marked in pretreated than in untreated atria. 6 Amoxapine inhibited the slow action potentials and contractions induced by isoprenaline in Kdepolarized atria. 7 It is concluded that the electrophysiological effects of amoxapine on rat atrial fibres are similar to those described for other tricyclic antidepressants. Possible explanations for the lower cardiodepressant activity of amoxapine are discussed.

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Section: Discussionmentioning

confidence: 76%

“…Moreover, very recently Manzanares & Tamargo (1982) have demonstrated that the inhibition of the fast inward Na current induced by imipramine was potentiated in rats chronically treated with imipramine. Unfortunately, the electrophysiological effects of amoxapine have not been previously studied in isolated cardiac fibres.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological effects of amoxapine in untreated and in amoxapine‐pretreated rat atria

Delgado

Manzanares

Tamargo

et al. 1986

British J Pharmacology

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“…The effects of imipramine on action potential duration (APD) show important species dependence. In bovine ventricular [ 75 ] and Purkinje fibers [ 65 ], guinea-pig papillary muscles [76][77] and isolated ventricular myocytes [ 70 ] imipramine shortened the APD, whereas in rabbit and rat atrial fibers [78][79] it lengthened the APD. The different effects of imipramine on APD can be explained by the important differences in the ionic currents responsible for the repolarization among animal species.…”

Section: Cellular Electrophysiological Effects Of Tcas-mentioning

confidence: 99%

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

Pacher¹,

Kecskeméti

2004

CPD

339

218

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The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na + , Ca 2+ and K + channels often leading to life-threatening arrhythmia.To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors.Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na + , Ca 2+ and K + channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders.The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon.

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“…TCAs are also known to have a local anaesthetictype action on peripheral excitable tissue (Ritchie & Greengard, 1961;Seeman et al, 1974;Schauf et al, 1975;Wang et al, 1981;Manzanares & Tamargo, 1983). This has led to the 'impulse blocking' hypothesis of antidepressant action (Randal, 1981), although it has generally been considered that concentrations of TCAs above the therapeutic range were necessary for neuronal block.…”

Section: Introductionmentioning

confidence: 99%

Frequency‐dependent block of field potentials in the rat hippocampal slice caused by tricyclic antidepressants

Anwyl

Rowan

1985

British J Pharmacology

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The effect of the tricyclic antidepressants imipramine and desipramine were studied on field potentials in the rat hippocampal slice. The electrically evoked stratum radiatum nerve volley, excitatory postsynaptic potential (e.p.s.p.) and pyramidal cell layer population spike (PS) were recorded in the CA1 region. At concentrations of 10−6 M to 10−5 M, impramine did not affect the amplitude of the nerve volley, e.p.s.p. or PS at low frequencies of stimulation (0.01 Hz). At higher frequencies of stimulation (1–100 Hz), imipramine caused a frequency‐dependent block of the nerve volley, e.p.s.p. and PS. The time course of onset of the frequency‐dependent block in the presence of imipramine was very slow. Maximum inhibition was reached after 3–4 h treatment with imipramine. Desipramine (10−6–10−5 M) also caused a frequency‐dependent block of the hippocampal field potentials. Only slight frequency‐dependent block was observed in slices from rats injected in vivo with desipramine (10 mg kg−1) for 14 days.

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Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Cited by 15 publications

References 22 publications

Electrophysiological effects of amoxapine in untreated and in amoxapine‐pretreated rat atria

Electrophysiological effects of amoxapine in untreated and in amoxapine‐pretreated rat atria

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

Frequency‐dependent block of field potentials in the rat hippocampal slice caused by tricyclic antidepressants

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