The psychotropic effects of cycloserine: A new use for an antibiotic

Crane, George E.

doi:10.1016/s0010-440x(61)80007-2

Cited by 53 publications

(31 citation statements)

References 5 publications

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“…Antidepressant effects of d-cycloserine were first noted in the 1950s. [4][5][6] However, double-blind, placebo-controlled studies at high doses were not conducted until recently. 7 A large, betweengroup, large effect-size (d = 0.91, P = .005) difference was seen in unipolar depression, corresponding to a mean 48% reduction in symptoms.…”

Section: See Commentary By Iosifescu P738mentioning

confidence: 99%

Single-Dose Ketamine Followed by Daily <span style="font-variant:small-caps; ">d</span>-Cycloserine in Treatment-Resistant Bipolar Depression

Kantrowitz¹,

Halberstam²,

Gangwisch³

2015

J. Clin. Psychiatry

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Section: See Commentary By Iosifescu P738mentioning

confidence: 99%

Single-Dose Ketamine Followed by Daily <span style="font-variant:small-caps; ">d</span>-Cycloserine in Treatment-Resistant Bipolar Depression

Kantrowitz¹,

Halberstam²,

Gangwisch³

2015

J. Clin. Psychiatry

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“…The original observations date back to the early 1960s, with the observation that tuberculosis patients treated with D-cycloserine at NMDAR antagonist doses showed clinical improvement. 164 At the time, interactions of D-cycloserine with NMDAR had not yet been described, and the observation with D-cycloserine was ignored in favor of monoamine oxidase inhibitors. Since then, other noncompetitive and competitive NMDAR antagonists were also shown to have antidepressant like effects in animal models, although clinical utility of these agents is limited by psychotogenic potential in humans.…”

Section: Depressionmentioning

confidence: 99%

Glutamate as a therapeutic target in psychiatric disorders

2004

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Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Glutamatergic neurotransmission may be modulated at multiple levels, only a minority of which are currently being exploited for pharmaceutical development. Ionotropic receptors for glutamate are divided into N-methyl-D-aspartate receptor (NMDAR) and AMPA receptor subtypes. NMDAR have been implicated in the pathophysiology of schizophrenia. The glycine modulatory site of the NMDAR is currently a favored therapeutic target, with several modulatory agents currently undergoing clinical development. Of these, the full agonists glycine and D-serine have both shown to induce significant, large effect size reductions in persistent negative and cognitive symptoms when added to traditional or newer atypical antipsychotics in double-blind, placebo-controlled clinical studies. Glycine (GLYT1) and small neutral amino-acid (SNAT) transporters, which regulate glycine levels, represent additional targets for drug development, and may represent a site of action of clozapine. Brain transporters for D-serine have recently been described. Metabotropic glutamate receptors are positively (Group I) or negatively (Groups II and III) coupled to glutamatergic neurotransmission. Metabotropic modulators are currently under preclinical development for neuropsychiatric conditions, including schizophrenia, depression and anxiety disorders. Other conditions for which glutamate modulators may prove effective include stroke, epilepsy, Alzheimer disease and PTSD. Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Approximately 60% of neurons in the brain, including all cortical pyramidal neurons and thalamic relay neurons, utilize glutamate as their primary neurotransmitter. 1 As a result, virtually all thalamocortical, corticocortical and corticofugal neurotransmission in the brain is mediated by glutamate. Glutamate is released from presynaptic terminals in response to neuronal depolarization, and is recycled by excitatory amino acid (EAA) transporters located on both neurons and glia. 2 Within glia, glutamate is converted to glutamine and released into extracellular fluid from which it is reabsorbed into presynaptic terminals and converted back to glutamate via action of neuronal glutaminase. Up to 2/3 of brain energy metabolism is related to reuptake and recycling of glutamate. 3 As such, functional imaging modalities, such as PET and fMRI, indexing activity primarily of brain glutamatergic systems. 4 The exchange of glutamine from glia to neurons is accomplished by coordinated actions of two transport systems, systems N and A, both of which are members of sodium-dependent neutral amino acid (SNAT) family of transporters. 5 These transport systems also transport precursors for cysteine and glycine, which are precursors to glutathione synthesis. 6 As these transporters are electrogenic, glutamate transporters may also participate in cellular signaling. 7 As with glutamate and GABA transporters, these recycling systems may constitute interesti...

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“…The initial clue came from studies of D-cycloserine (DCS), an antibiotic developed to treat tuberculosis. 42 In preclinical studies, DCS, at maximally stimulating doses, produces roughly half of the maximal facilitation of NMDA receptor function associated with glyMolecular Psychiatry cine. 43,44 Under conditions where the occupancy of glycine-B sites by agonists exceeds 50%, glycine-B antagonist-like effects emerge.…”

Section: Glutamatergic Abnormalities In Mood Disordersmentioning

confidence: 99%

“…45 This antagonist-like effect of DCS is reflected in an increase in the off-rate for glutamate from the NMDA receptor. 46 Crane 42,47 reported evidence of DCS antidepressant effects in depressed tuberculosis patients. Beneficial effects of DCS in doses of 500 mg day −1 occurred in a high proportion of the patients studied with respect to depressed mood, insomnia and reduced appetite.…”

Section: Glutamatergic Abnormalities In Mood Disordersmentioning

confidence: 99%

Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments

et al. 2002

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Glutamate and ␥-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders. Molecular Psychiatry (2002) 7, S71-S80.

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The psychotropic effects of cycloserine: A new use for an antibiotic

Cited by 53 publications

References 5 publications

Single-Dose Ketamine Followed by Daily <span style="font-variant:small-caps; ">d</span>-Cycloserine in Treatment-Resistant Bipolar Depression

Single-Dose Ketamine Followed by Daily <span style="font-variant:small-caps; ">d</span>-Cycloserine in Treatment-Resistant Bipolar Depression

Glutamate as a therapeutic target in psychiatric disorders

Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments

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