ABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the effects of high-dose oral glycine on positive and negative symptoms and cognitive function when added to clozapine in adults with schizophrenia. METHOD: The authors conducted a double-blind, placebo-controlled, parallel-group trial of 60 g/day of glycine added to clozapine for 8 weeks in 30 adults with schizophrenia. Clinical ratings were performed every 2 weeks. RESULTS: Twenty-seven patients completed the trial. Glycine augmentation of clozapine produced no statistically significant change in positive or negative symptoms or cognitive functioning. No subjects showed clinically significant worsening of clinical ratings. CONCLUSIONS: These data, combined with data from previous trials with D-cycloserine and glycine, suggest that agonists at the glycine site may be less effective when combined with clozapine than they are when combined with conventional antipsychotics.
Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Glycine/therapeutic use , Schizophrenia/drug therapy , Adult , Ambulatory Care , Antipsychotic Agents/administration & dosage , Cognition Disorders/drug therapy , Cognition Disorders/psychology , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Glycine/administration & dosage , Humans , Male , Placebos , Psychiatric Status Rating Scales/statistics & numerical data , Schizophrenia/diagnosis , Schizophrenic Psychology , Treatment OutcomeABSTRACT
The gastrin-releasing peptide receptor (GRP-R) is one of three members of the mammalian bombesin subfamily of seven-transmembrane G protein-coupled receptors that mediate diverse biological responses including secretion, neuromodulation, chemotaxis, and growth. The X chromosome-linked GRP-R gene is expressed widely during embryonic development and predominantly in gastrointestinal, neuronal, and neuroendocrine systems in the adult. Surprisingly, gene-targeted mice lacking a functional GRP-R gene develop and reproduce normally and show no gross phenotypic abnormalities. However, peripheral administration of bombesin at dosages up to 32 nmol/kg to such mice had no effect on the suppression of glucose intake, whereas normal mice showed a dose-dependent suppression of glucose intake. These data suggest that selective agonists for the GRP-R may be useful in inducing satiety.
Subject(s)
Bombesin/pharmacology , Eating/drug effects , Receptors, Bombesin/deficiency , Satiation/physiology , Amylases/metabolism , Animals , Carbachol/pharmacology , Dose-Response Relationship, Drug , Mice , Mice, Mutant Strains , Pancreas/drug effects , Receptors, Bombesin/agonists , Receptors, Bombesin/genetics , Sincalide/pharmacologyABSTRACT
The excitatory amino acids, glutamate and aspartate, are of interest to schizophrenia research because of their roles in neurodevelopment, neurotoxicity and neurotransmission. Recent evidence suggests that densities of glutamatergic receptors and the ratios of subunits composing these receptors may be altered in schizophrenia, although it is unclear whether these changes are primary or compensatory. Agents acting at the phencyclidine binding site of the NMDA receptor produce symptoms of schizophrenia in normal subjects, and precipitate relapse in patients with schizophrenia. The improvement of negative symptoms with agents acting at the glycine modulatory site of the NMDA receptor, as well as preliminary evidence that clozapine may differ from conventional neuroleptic agents in its effects on glutamatergic systems, suggest that clinical implications may follow from this model. While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia.
