Effect of desipramine and pargyline on brain gamma-aminobutyric acid

Patel, Girish J.; Schatz, Robert; Constantinides, S; Lal, Harbans

doi:10.1016/0006-2952(75)90313-5

Cited by 27 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this connection, Korf and Venema reported that desipramine produce a reversible increase in the release of endogenous GABA from the exposed rat thalamus, and this effect of desipramine was Ca-dependent (30). Furthermore, desipramine markedly increases the GABA concentration in whole mouse brain (31). These previous findings and our present results strongly support the idea that desipramine produce a variety of pharmacological effects, including antidepressive action and analgesic action, through activating GABAergic systems.…”

Section: Discussionsupporting

confidence: 90%

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Asahi

Yonehara

2001

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-We have conducted this study to elucidate the influence of GABAergic systems on manifestation of pharmacological activity of desipramine using both pharmacological and electrophysiological methods. Desipramine (20 mg /kg, i.p.) significantly blocked the adjuvant-induced thermal hyperalgesia, which was facilitated by treatment with the GABAA antagonist picrotoxin (2 mg/ kg, i.p.) or the GABAB antagonist saclofen (2 mg/kg, i.p.). This analgesic effect of desipramine was antagonized by post-treatment with picrotoxin or saclofen. However, none of these compounds showed any effect in normal animals without adjuvant-induced inflammation. In a slice preparation of the hippocampus, treatment with GABA (10 -5 -5´10 -4 M), baclofen (10 -5 -10 -4 M) or muscimol (10 -5 -10 -4 M) inhibited the field potential evoked in pyramidal neurons by Schaffer collateral stimulation. The inhibitory effect of GABA was facilitated by concurrent application of desipramine, carbamazepine or diazepam at a concentration of 5´10-5 -2´10 -4 M. The rank of order of facilitation is: desipramine > carbamazepine > diazepam. Desipramine also enhanced the inhibitory effect of baclofen and muscimol. These results suggest that desipramine causes GABAergic systems to activate still more, and this phenomenon appears to be involved in manifestation of the pharmacological activity of desipramine such as antinociception.

show abstract

Section: Discussionsupporting

confidence: 90%

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Asahi

Yonehara

2001

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Elevated GABA levels and enhanced GABA release following high dose acute administration of tricyclic antidepressants, MAOIs and daily electroconvulsive shock were reported in several early rodent studies [84][85][86][87][88][89]. However, other studies have found GABA levels to be generally unaltered by antidepressant administration [72,90].…”

Section: Gabaergic Effects Of Existing Antidepressant Medicationsmentioning

confidence: 99%

GABAergic Contributions to the Pathophysiology of Depression and the Mechanism of Antidepressant Action

Sanacora

Sarıçiçek²

2007

CNSNDDT

117

View full text Add to dashboard Cite

Increasing evidence suggests that abnormalities in amino neurotransmission are associated with the neurobiology of depression. Preclinical studies demonstrate that GABA modulating agents are active in commonly used rodent behavioral models of antidepressant activity, and that chronic administration of antidepressant drugs induces marked changes in GABAergic function. In humans, depressed patients have lower plasma, CSF and brain GABA concentrations than non-depressed comparison subjects. The recent discovery that several anticonvulsant and GABA-mimetic agents possess mood stabilizing and antidepressant properties has further increased interest in these findings. This review outlines the existing literature investigating the possible involvement of GABA in the neurobiology of depression and briefly highlights how this information may afford new targets for antidepressant drug development.

show abstract

“…For example, GABA levels in the occipital cortex were increased in depressed patients after antidepressant treatments such as electroconvulsive therapy (ECT) or selective serotonin reuptake inhibitors (SSRIs; Sanacora et al, 2002; Sanacora et al, 2003) but not after cognitive behavioral therapy (Sanacora et al, 2006). Moreover, a number of earlier animal studies reveal that administration of tricyclic antidepressant drugs, inhibitors of monoamine oxidase, or electroconvulsive shock elevates GABA levels or increases its release (Bowdler et al, 1983; Korf and Venema, 1983; Patel et al, 1975; Perry and Hansen, 1973; Popov and Matthies, 1969). Collectively, these data clearly indicate a relationship between antidepressant medication and regulation of GABAergic transmission.…”

Section: Introductionmentioning

confidence: 99%

Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression

Karolewicz

Maciąg

O'Dwyer

et al. 2009

Int. J. Neuropsychopharm.

173

View full text Add to dashboard Cite

Accumulating evidence suggests dysfunction of the gamma-aminobutyric acid (GABA) system in major depressive disorder (MDD). Neuroimaging studies consistently report reductions of cortical GABA in depressed patients. Our post-mortem analyses demonstrate a reduction in the density and size of GABAergic interneurons in the dorsolateral prefrontal cortex (PFC) in MDD. The goal of this study was to test whether the level of glutamic acid decarboxylase (GAD), the GABA synthesizing enzyme, will also be reduced in the same cortical region in MDD. Levels of GAD-65 and GAD-67 proteins were investigated by Western blotting in samples from the dorsolateral PFC (BA9) in 13 medication-free subjects with MDD, and 13 psychiatrically healthy controls. The overall amount of GAD-67 was significantly reduced (−34 %) in depressed subjects as compared to matched controls. Since recent neuroimaging studies demonstrate that antidepressants modulate GABA levels, additional experiments were performed to examine the levels of GAD in 8 depressed subjects treated with antidepressant medications. Levels of GAD-67 were unchanged in these depressed subjects as compared to their respective controls (n=8). The overall amounts of GAD-65 were similar in depressed subjects compared to matched controls, regardless of antidepressant medication. Reduced levels of GAD-67, which is localized to somata of GABA neurons, further support our observation of a decreased density of GABAergic neurons in the PFC in depression. It is likely that a decrease in GAD-67 accounts for the reduction in GABA levels revealed by neuroimaging studies. Moreover, our data support previous neuroimaging observations that antidepressant medication normalizes GABA deficits in depression.

show abstract

Effect of desipramine and pargyline on brain gamma-aminobutyric acid

Cited by 27 publications

References 15 publications

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

Involvement of GABAergic Systems in Manifestation of Pharmacological Activity of Desipramine

GABAergic Contributions to the Pathophysiology of Depression and the Mechanism of Antidepressant Action

Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression

Contact Info

Product

Resources

About