Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional

Summary: 
      Question #1: Will glycine ameliorate cognitive deficits? Hypothesis #1: Based on positive
      findings conducted with glycine and milacemide, a glycine prodrug, in schizophrenia and
      dementia, we expect that glycine will ameliorate cognitive deficits.

      Question #2: Will alcoholic patients show enhanced endocrinal effects to glycine? Hypothesis
      #2: Based on the dose-related effects of glycine in healthy subjects, we expect that glycine
      will increase the endocrinal response to glycine in alcoholic patients with, supposedly,
      dysregulated NMDA receptor function.

      Question #3: Will D-cycloserine have ethanol-like effects? Hypothesis #3: If inhibition of
      NMDA receptor function is fundamental to the subjective effects of ethanol, then the NMDA
      antagonist properties of D-cycloserine should be recognized as ethanol-like (relative to
      placebo) in recently detoxified alcoholics and healthy subjects.

      Question #4: Will D-cycloserine reverse cognitive benefits of glycine? Hypothesis 4: Based on
      the dose related NMDA antagonist activity of D-cycloserine, we expect that D-cycloserine will
      compete with the agonist activity of glycine and therefore it will reverse the cognitive
      benefits of glycine.

      Question #5: Will D-cycloserine inhibit endocrinal effects of glycine? Hypothesis #5: If the
      agonist activity of glycine is necessary to determine endocrine response, then the
      dose-related NMDA antagonist properties of D-cycloserine should block these effects.
    

Detailed description: 
      The purpose of this study is to investigate the interaction between glycine and D-cycloserine
      in alcoholic patients and healthy subjects. Preclinical studies have shown that compounds
      acting at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex, such as
      glycine, may reverse the effects of ethanol on the NMDA receptor function (Rabe et al.,
      1990). The amino acid glycine is a co-agonist of the NMDA receptor complex (Kemp et al.,
      1993). It binds to the strychnine-insensitive site and positively modulates the NMDA receptor
      (Mc Donald et al., 1990). Physiologically, the glycine site is not saturated, and
      administration of glycine can potentiate NMDA receptor mediated responses. In contrast,
      D-cycloserine (Hood et al., 1989) is a partial-agonist at the glycine site of the NMDA
      receptor, with dose-dependent NMDA antagonist properties. The NMDA antagonist activity of
      D-cycloserine should produce ethanol like-effects that can be reversed by the agonist
      glycine. This study is intended to evaluate possible contributions of the glycine site to the
      reduction of cognitive deficits of alcoholism and complements the current work at VA
      Connecticut Healthcare System on the NMDA antagonists in alcoholic and healthy subjects.
    

Intervention name(s): D-Cycloserine PO and Glycine IV; Placebo D-Cycloserine PO and placebo Glycine IV; Placebo D-Cycloserine PO and Glycine IV; D-Cycloserine PO and placebo Glycine IV
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Test days will involve administration of D-Cycloserine in the morning in pill form then 4 hours later a 30 minute infusion of Glycine.; Placebo
Other intervention name(s): Glycine infusion; Cycloserine; placebo
Intervention MeSH terms: Cycloserine; Glycine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Alcohol Dependence, Alcoholism, Glycine, D-Cycloserine