Glycine Adjuvant Therapy to Conventional Neuroleptic Treatment in Schizophrenia

Rosse, Richard B.; Theut, Susan K.; Banay‐Schwartz, M.; Leighton, Michael P.; Scarcella, Erminia; Cohen, Cynthia; Deutsch, Stephen I.

doi:10.1097/00002826-198910000-00006

Cited by 96 publications

(37 citation statements)

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“…There were 27 randomized placebo-controlled doubleblind studies (2,6,7,10-12,14,23,25-42), 8 non-randomized trials (43)(44)(45)(46)(47)(48)(49)(50)(51), and 1 case report. Except for two trials (42,49) with drug-free patients, all other studies involved adjuvant therapy for antipsychotic treatment.…”

Section: Resultsmentioning

confidence: 99%

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Chaves

Marque

Trzesniak

et al. 2009

Braz J Med Biol Res

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Section: Resultsmentioning

confidence: 99%

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Chaves

Marque

Trzesniak

et al. 2009

Braz J Med Biol Res

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“…Finally, glycine has several beneficial effects that would justify its clinical use: it can be administered in the diet without apparent side-effects, as suggested by Rosse et al (43) and Carvajal-Sandoval et al (13).…”

Section: Discussionmentioning

confidence: 99%

Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats

Hafidi¹,

Pérez²,

Zamora³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

105

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os. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comp Physiol 287: R1387-R1393, 2004. First published August 26, 2004 doi:10.1152/ajpregu.00159.2004The study investigated the mechanism by which glycine protects against increased circulating nonesterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 wk, markedly reduced high BP in sucrose-fed rats (SFR) (122.3 Ϯ 5.6 vs. 147.6 Ϯ 5.4 mmHg in SFR without glycine, P Ͻ 0.001). Decreases in plasma triglyceride (TG) levels (0.9 Ϯ 0.3 vs. 1.4 Ϯ 0.3 mM, P Ͻ 0.001), intra-abdominal fat (6.8 Ϯ 2.16 vs. 14.8 Ϯ 4.0 g, P Ͻ 0.01), and adipose cell size were observed in SFR treated with glycine compared with SFR without treatment. Total NEFA concentration in the plasma of SFR was significantly decreased by glycine intake (0.64 Ϯ 0.08 vs. 1.11 Ϯ 0.09 mM in SFR without glycine, P Ͻ 0.001). In control animals, glycine decreased glucose, TGs, and total NEFA but without reaching significance. In SFR treated with glycine, mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the ␤-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or ␤-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension. obesity; mitochondrial oxygen uptake; fatty acid oxidation OBESITY is a significant human health problem; its incidence is reaching epidemic proportions in many Western countries (2, 31). Obesity with fat accumulation predominantly in the abdominal cavity is more frequently associated with disorders of glucose and lipid metabolism than is subcutaneous fat obesity (6, 17). It is well known that increased intra-abdominal fat accumulation is also associated with elevated circulating nonesterified fatty acids (NEFA) (33), resulting from the increased lipolytic activity in adipose tissue. High levels of circulating NEFA have been assumed to be a possible link between intra-abdominal fat accumulation and elevated blood pressure (BP) (9,34,46,49).Several factors are known to be involved in the development of intra-abdominal adiposity in both humans and animals, including genetic and environmental factors, such as excessive fat or carbohydrate intake and lack of physical exercise (8, 44). Thus several animal models of obesity have been developed to investigate the mechanism by which obesity induces hypertension, hyperinsulinemia, and insulin resistance.In our laboratory, we developed an animal model of intraabdominal fat accumulation, indu...

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“…The earliest studies in this regard used glycine in doses of 5-15 g day −1 and obtained inconsistent results. 107,108 In more recent work with glycine, higher doses were administered (30-60 g day −1 ) and more robust and consistent effects were found, primarily in the improvement of negative symptoms. [109][110][111] d-Cycloserine, a partial agonist at the glycine regulatory site on the NMDA receptor, has also been tested in schizophrenic patients.…”

Section: Therapeutic Potential Of Agonists Of the Glycine Site On Thementioning

confidence: 95%

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

1999

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Available evidence indicates that clozapine is the most effective antipsychotic currently used for the pharmacotherapy of schizophrenia. Unfortunately, clozapine can cause serious side effects that limit the use of the drug. The therapeutic mechanism of action of clozapine is poorly understood, and accordingly, it has been difficult to design new drugs with the advantageous therapeutic properties of clozapine. Based on hypotheses that dopaminergic and serotonergic receptor-blocking properties of clozapine account for its clinical efficacy, several novel antipsychotic drugs have been introduced recently. There is currently insufficient data to reach definitive conclusions regarding the efficacy of the newer 'atypical' antipsychotics in comparison to clozapine. However, most published studies, and general clinical impressions, suggest that none of the newer drugs are as effective as clozapine in treating patients resistant to typical antipsychotic drug therapy. The present paper briefly reviews the clinical experience with the newer 'atypical' antipsychotic drugs and then discusses clinical and preclinical data potentially relevant to mechanisms of action of clozapine in relation to the NMDA receptor hypofunction hypothesis of schizophrenia.Keywords: clozapine; olanzapine; risperidone; ziprasidone; quetiapine; antipsychotic; schizophrenia; dopamine; NMDA The introduction of clozapine for the pharmacotherapy of schizophrenia represented a significant advance in the treatment of this devastating mental illness. Clozapine is superior to typical neuroleptic drugs (eg haloperidol) in treating positive and negative symptoms, and is effective in many patients who are refractory to typical antipsychotics. [1][2][3] In addition, clozapine does not induce the extrapyramidal side effects (EPS) commonly caused by the typical agents. Because of these properties, clozapine was termed atypical and represents the prototype drug of this class. Although clozapine is the most efficacious antipsychotic currently available, serious side effects induced by the drug, including agranulocytosis, impose substantial limitations on its use. Concerted research and development efforts have been made to produce an antipsychotic drug with the therapeutic advantages of clozapine, without the properties contributing to its serious side effects. However, the specific pharmacological characteristics of clozapine that confer its therapeutic properties are poorly understood. Clozapine binds to a diverse number of neurotransmitter receptors (see Table 1) but it is unclear whether actions at specific serotonin, dopamine, or adrenergic receptors, alone or in combination, account for its clinical efficacy.A number of specific hypotheses concerning mechanisms of action of clozapine have directed drug discovery efforts and led to clinical trials of drugs with widely different receptor-binding characteristics. The clinical experience with drugs whose development was inspired by clozapine will be briefly reviewed and then actions of clozapine and other antip...

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Glycine Adjuvant Therapy to Conventional Neuroleptic Treatment in Schizophrenia

Cited by 96 publications

References 0 publications

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

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