Posted by Phidippus on December 31, 2009, at 16:10:19
In reply to Re: putting all my hopes on Glycine ..., posted by Jeroen on December 31, 2009, at 15:58:33
There's a lot of positive literature on Glycine, but most of it focuses on using Glycine to treat the negative symptoms of schizophrenia:
Glycine and Glycine-like Compounds
Increasing NMDA function with glycine agonists may be a potential new strategy for the management of schizophrenia (22), particularly for the treatment of negative symptomatology (34,38). Since the conventional, DA-blocking antipsychotics are generally not effective for negative symptoms, augmentation of therapeutic effects with glycine and glycine-like compounds may be an effective treatment alternative.An open study by Waziri et al. (80) was one of the first to report that glycine has antipsychotic properties. Eleven schizophrenic patients were given high doses (525 g/day) of glycine in addition to treatment with typical neuroleptics. Clinical improvement was observed in 4/11 patients and was maintained after the neuroleptics were withdrawn. An open study by Costa et al. (16) reported improvement in two of six chronic schizophrenic patients treated with glycine (15 g/day) and typical neuroleptics. In another open investigation, Rosse et al. (69) administered glycine (10.8 g/day) to six chronic schizophrenics and observed improvement in BPRS and SANS ratings in three of the patients. Potkin et al. (66) reported improvement in two of 11 patients maintained on neuroleptics and treated with glycine (15 g/day) in a double-blind, placebo-controlled study. Heresco-Levy et al. (34) administered high-dose glycine (0.8 g/kg) as adjuvant therapy in a double-blind, placebo-controlled crossover trial. Improvement in negative symptoms (PANSS) was observed only after six weeks of glycine treatment in 8/11 patients; improvement was maintained after glycine was withdrawn. Measurements of glycine levels revealed that those patients with the lowest pretreatment levels showed the most improvement in negative symptoms. One of the most convincing pieces of data for the antipsychotic effects of glycine is from a double-blind, placebo-controlled study by Javitt et al. (38) which showed that high doses of glycine (30 g/day) improved negative symptoms in all seven of the neuroleptic-treated schizophrenics in the study.
Other glycine-related compounds administered to schizophrenics include milacemide, an acylated "prodrug" of glycine that is converted into glycine in the brain (68), and D-cycloserine, a partial agonist at the glycine site (13,28). Open studies of "low" and "high" dose milacemide by Rosse et al. (69) showed no significant therapeutic effects of the drug. Data from an increasing number of studies suggest that D-cycloserine may be effective in a narrow dose range (e.g., 50100 mg) in the treatment of negative symptoms (28,29,18,79). However, one open study by Cascella et al. (13) used high doses of milacemide (250 mg), which produced improvement in 1/7 patients and clinical worsening in 4/7 patients. Dramatic improvement in negative symptoms was seen in five of nine patients in a dose-finding trial (28). A more recent study (29) of 50 schizophrenic outpatients in an eight week, placebo-controlled trial showed that SANS scores were reduced by 20% in the D-cycloserine-treated group, specifically on the subscales measuring flat affect and anhedonia. DeSouza et al. (18) similarly observed an improvement in negative symptoms after treatment with D-cycloserine. Finally, a single-blind study in drug-free schizophrenics showed that D-cycloserine-treated patients had significant reductions in negative symptoms (79).
Glycine Transport Inhibitors
The identification of glycine transport inhibitors provided a new and exciting approach to the development of alternative antipsychotic compounds (5). Two classes of glycine transporters have been cloned and identified. These are GlyT1 and related subunits (GlyT1a-c), which are present in forebrain and colocalize with NMDA-R, and Gly T2, found in spinal cord and brain stem, and which colocalizes with strychnine-sensitive glycine receptors. The glycine transporters are high-affinity and regulate extracellular glycine. Inhibitors to the Gly transporters have been identified. Of these, the most potent is TxRx 5311 which is active at the GlyT1c receptors. In vivo experiments in rats showed that the GlyT1 transport inhibitors decreased PCP-induced increases in locomotor activity. Research data suggests that these compounds are selective for NMDA-R channel activity, the site where PCP is active (5). These substrates may be more effective than glycine in the treatment of schizophrenia (39). Since schizophrenic patients with low pretreatment glycine levels are the most likely to respond to glycine agonists (34), this subgroup of patients may be particularly good responders to treatment with glycine transport inhibitors.
poster:Phidippus
thread:931579
URL: http://www.dr-bob.org/babble/20091227/msgs/931840.html