Effects of clozapine on the activity of central dopaminergic and noradrenergic neurons

M, Souto; Monti, J.M.; Altier, H.

doi:10.1016/0091-3057(79)90160-6

Cited by 37 publications

(18 citation statements)

References 9 publications

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“…These findings are congruent with previous electrophysiological studies of other APDs, which show that both haloperidol and clozapine increase LC neuronal firing rates (Souto et al 1979;Dinan and Aston-Jones 1984;Nilsson et al 2005). However, in similarity with its effect on dopaminergic neurons, a dose of asenapine (0.025 mg/kg i.v.)…”

Section: Discussionsupporting

confidence: 93%

Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms

et al. 2009

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Asenapine at doses associated with antipsychotic activity enhanced cortical monoamine efflux. Whereas the asenapine-induced dopamine increase in nucleus accumbens is dependent on activation of dopaminergic neurons in the VTA, the increase of cortical dopamine outflow involves largely a local action at nerve terminals. Our data provide further insight on the pharmacologic characteristics of asenapine that may have bearing on its clinical efficacy in the treatment of schizophrenia and bipolar disorder.

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Section: Discussionsupporting

confidence: 93%

Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms

et al. 2009

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“…In addition, it has been shown that the i.v. administration of CLOZ produces a n increase in the basal firing rate of A10 (Hand et al, 1987a,b;Souto et al, 1979) and A9 DA cells (Souto et al, 1979), or no change (Bunney and Aghajanian, 1975). Currently, the exact discrepancy between these studies is unknown, but could be related to the sampling of different DA cell populations, as there are differences between studies with regard to stereotaxic coordinates.…”

Section: Electrophysiological Studiesmentioning

confidence: 96%

“…In addition, in vivo electrophysiological studies have shown that the i.v. administration of CLOZ produces a significant increase in the basal firing rate of spontaneously active NE neurons in the locus coeruleus (Rasmussen and Aghajanian, 1988;Itamirez and Wang, 1986;Souto et al, 1979), and that the suppression of NE cell firing produced by d-amphetamine is blocked by CLOZ (Souto et al, 1979). Corresponding to the results obtained from electrophysiological studies, the systemic administration of CLOZ produces an increase in NE turnover (Bartholini, 1976;Bartholini et al, 1972Bartholini et al, ,1973Braestrup and Nielsen, 1976;Burki et al, 1974GroS and Schumann, 1980;McMillan and Shore, 1978;Sulser and Robinson, 1978).…”

Section: Cx2 Adrenergic Receptorsmentioning

confidence: 99%

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Ashby

Wang

1996

Synapse

167

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Clozapine [8-chloro- 11-(4-methyl- 1-piperazinyl)-3H-dibenzo (b,e)(1,4) diazepine], or clozaril, is a member of the dibenazepine class of antipsychotic drugs. Initially, studies in animals using a number of neurochemical, biochemical, electrophysiological, and behavioral paradigms indicated that clozapine was markedly different from various typical antipsychotic drugs such as haloperidol and chlorpromazine. Subsequently, clinical studies have shown that clozapine is effective in ameliorating the core symptoms, as well as the negative symptoms, in schizophrenia. However, clozapine has a much lower propensity for inducing neurological side effects after acute or repeated administration compared to various typical neuroleptics. Furthermore, clozapine is therapeutically effective in treating about 30% of schizophrenic patients who are resistant to standard antipsychotic drugs. Based on the above information, clozapine has been designated an atypical antipsychotic drug. However, at this time, it is not entirely clear why clozapine is such a unique antipsychotic drug. To date, there has not been a comprehensive review regarding clozapine's pharmacological profile. Therefore, we will review clozapine's profile in the following areas: 1) affinity for neurotransmitter receptors in the brain; 2) electrophysiology (in vivo, single-cell recording and iontophoresis; in vitro studies); 3) in vivo microdialysis and voltammetry; 4) monoamine turnover or metabolism; 5) intermediate early gene expression; 6) positron emission tomography studies; and 7) molecular biological studies. We will also compare and contrast clozapine's acute and chronic effects, and discuss the merits of various hypotheses that have been put forward to explain clozapine's unique profile.

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“…ment of plateau 3 H-DHPG concentrations during 3 H-NE infusion (Eisenhofer et al 1991), and in the present study, clozapine treatment did not alter the slowly progressive increase in plasma 3 H-DHPG levels. Clozapine produces blockade of ␣1 and ␣2 adrenoceptors (Arbilla et al 1978;Souto et al 1979;Richelson and Nelson 1984;Baldessarini and Frankenburg 1991). These actions could increase sympathoneural outflows reflexively in response to systemic vasodilation and also augment NE release for a given amount of nerve traffic, by blocking inhibitory modulatory ␣2-adrenoceptors on sympathetic nerves (Breier et al 1994b;Breier 1994).…”

Section: Figure 2 [ 3 H]dhpg/[ 3 H]-ne Ratio Inmentioning

confidence: 99%

Mechanism of Peripheral Noradrenergic Stimulation by Clozapine

Elman

Goldstein

Eisenhofer

et al. 1999

Neuropsychopharmacology

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Elevated plasma norepinephrine (NE) levels is a relativelyClozapine is an atypical neuroleptic with efficacy superior to that of conventional antipsychotic agents (Kane et al. 1988;Leiberman et al. 1989;Breier et al. 1994a;Breier et al. 1994b;Meltzer 1995;Meltzer et al. 1996). A relatively consistent clinical effect of clozapine is a robust increase in norepinephrine (NE) levels, both in cerebrospinal fluid (CSF) (Ackenheil 1989;Leiberman et al. 1989;Leiberman et al. 1991;Pickar et al. 1992) and in plasma (Pickar et al. 1992;Green et al. 1993;Davidson et al. 1993;Breier et al. 1994b;Breier 1994;Brown et al. 1997). Plasma NE increases have been related to clinical improvement (Breier et al. 1994b;Breier 1994), suggesting that this neurochemical effect may be involved in clozapine's therapeutic mechanism of action. In contrast, traditional antipsychotic agents studied to date have no or negligible influence on NE levels (Pickar et al. 1992;Breier et al. 1994b;Brown et al. 1997).The mechanism of clozapine-induced NE elevation has not been established. Plasma levels of any endogenous biochemical represent the ratio of the rate of release of the substance into the bloodstream (spillover) and clearance of the substance from the bloodstream. Clozapine-induced elevations in plasma NE levels, therefore, could result from increased spillover, deceased clearance, or a combination of both.Neuronal uptake by sympathetic nerves constitutes a determinant of plasma NE spillover (Eisenhofer et al. 1996) and clearance (Esler et al. 1981;Eisenhofer et al. 1991). After neuronal uptake of NE, some of the NE in the axoplasm undergoes oxidative deamination by mitochondrial monoamine oxidase (MAO), forming dihy-

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Effects of clozapine on the activity of central dopaminergic and noradrenergic neurons

Cited by 37 publications

References 9 publications

Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms

Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Mechanism of Peripheral Noradrenergic Stimulation by Clozapine

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