Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord.
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In the present study we tested the effects of the antihyperalgesic compound gabapentin on dorsal horn neurones in adult spinal cord. Slices were taken from control and hyperalgesic animals suffering from streptozocin-induced diabetic neuropathy. At concentrations up to 100 microM, bath application failed to affect the resting membrane properties of dorsal horn neurones taken from both groups of animal. In contrast, bath application of gabapentin dramatically reduced the magnitude of the excitatory postsynaptic current (EPSC) in neurones taken from hyperalgesic animals without altering the magnitude of the EPSC in control animals. Using a paired pulse stimulation protocol, together with analysis of miniature EPSC's, it was possible to demonstrate that gabapentin mediated these effects via a pre-synaptic site of action. (+info)
The effects of lamotrigine on the pharmacokinetics of lithium.
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AIMS: The treatment of bipolar disorder often includes use of multiple drug therapies. Lithium is one of the most commonly used treatments, but has a narrow therapeutic window. Lamotrigine, an established antiepileptic drug, is emerging as a potentially important new therapy in the treatment of bipolar disorder. The objective of this two-treatment crossover study was to determine whether lamotrigine affects lithium pharmacokinetics. METHODS: Twenty healthy adult men completed the study. Subjects took 2 g lithium gluconate anhydrous every 12 h in the morning and evening for 5 days and in the morning of day 6, with or without 100 mg lamotrigine once daily in the morning for 6 days. Blood and urine samples were collected on day 6 of both treatments to characterize the pharmacokinetics of lithium using noncompartmental methods. RESULTS: The geometric least-square mean ratio for renal clearance of lithium between the combination treatment and lithium alone treatment was 0.93 (95% confidence interval 0.85-1.02). Both treatments were well tolerated. CONCLUSIONS: Lamotrigine does not cause significant change in the pharmacokinetics of lithium. (+info)
Steady-state pharmacokinetics of lithium in healthy volunteers receiving concomitant meloxicam.
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AIMS: This open, controlled study investigated the effect of concomitant 15 mg oral meloxicam on the pharmacokinetics of lithium in healthy male volunteers. METHODS: On days 1-14 lithium was coadministered with meloxicam to 16 volunteers; on days 10-14 lithium was administered in individualized dosage regimes to achieve stable lithium plasma concentrations in the lower therapeutic range of 0.3-0.7 mmol l(-1). A 12 h steady-state concentration profile for lithium was obtained at day 14, after which meloxicam was withdrawn. The lithium dose remained unchanged from day 15 to day 22, at which time a second lithium concentration profile was determined. RESULTS: Lithium and meloxicam were well tolerated throughout the study and all 16 volunteers completed the study. Lithium predose concentrations (Cpre,ss) and area under the curve (AUCss) values both increased by 21% (paired t-test P = 0.0002; 90% confidence intervals for test/reference ratios: 113-130% and 115-128%, respectively) when lithium was coadministered with meloxicam compared with values obtained for lithium alone. The geometric mean lithium Cpre,ss was 0.65 mmol l(-1) when coadministered with meloxicam and 0.54 mmol l(-1) for lithium alone. Lithium Cmax,ss values were increased by 16% by coadministration of meloxicam, from 0.97 mmol l(-1) to 1.12 mmol l(-1). The total plasma clearance of lithium was lower with concomitant meloxicam administration (82.5% of value for lithium alone). CONCLUSIONS: Meloxicam (15 mg) moderately increased the plasma concentration of lithium in healthy volunteers, but by a magnitude thought to be of low clinical relevance. Nevertheless, lithium plasma concentrations should be closely monitored in patients receiving concomitant meloxicam and lithium therapy. (+info)
Management of bipolar disorder.
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Bipolar disorder most commonly is diagnosed in persons between 18 and 24 years of age. The clinical presentations of this disorder are broad and include mania, hypomania and psychosis. Frequently associated comorbid conditions include substance abuse and anxiety disorders. Patients with acute mania must be evaluated urgently. Effective mood stabilizers include lithium, valproic acid and carbamazepine. A comprehensive management program, including collaboration between the patient's family physician and psychiatrist, should be implemented to optimize medical care. (+info)
Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.
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OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder. (+info)
Effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients symptomatically stable on lithium.
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BACKGROUND: Previous studies suggest that brain serotonin neurotransmission may mediate the actions of lithium carbonate. Acute tryptophan depletion reduces brain serotonin and allows the study of this neurotransmitter in patient groups. AIMS: To examine the effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients who were symptomatically stable on lithium. METHOD: Nineteen subjects satisfying DSM-IV criteria for bipolar I disorder participated in a within-subject, double-blind, placebo-controlled random-order crossover study. Symptoms were evaluated following acute tryptophan depletion, which was induced by a 100 g amino acid drink following an overnight fast. RESULTS: Plasma tryptophan fell significantly after the depleting drink, but not after the control drink (P < 0.05, paired t-test, mean reduction 83%). No significant changes in mood or suicidality scores were recorded after acute tryptophan depletion. CONCLUSIONS: Acute tryptophan depletion does not reverse lithium's effects on mood and suicidality in bipolar disorder. (+info)
Variability of erythrocyte and serum lithium levels correlates with therapist treatment adherence efforts and maintenance treatment outcome.
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This study investigated the relationship between psychotherapeutic interventions and pharmacologic measures of pharmacotherapy treatment adherence in patients with bipolar I disorder, as well as the relationship between these measures and treatment outcome. Subjects were participating in an ongoing maintenance treatment study. Audiotaped therapy sessions were rated for frequency of psychotherapeutic interventions related to pharmacotherapy treatment adherence. Pharmacologic measures of medication adherence were compared to the tape ratings as well as to treatment outcome. Variability in log erythrocyte (RBC) lithium-a marker of probable nonadherence to the pharmacotherapy regimen-for individual patients correlated significantly with treatment adherence interventions scale ratings. This marker of nonadherence was significantly related to maintenance treatment outcome, as was variability of the serum lithium level/dose (L/D) ratio; however, no relationship was found between treatment adherence interventions scale ratings and outcome. (+info)
Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca(2+)- and K(+)-evoked serotonin release.
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To elucidate mechanisms of hippocampal serotonin release and possible mechanisms of clinical action of carbamazepine (CBZ), we determined interaction between antagonists of N-type (omega-conotoxin GVIA:GVIA), P-type (omega-agatoxin IVA:IVA) Ca(2+) channels, Na(+) channel (tetrodotoxin: TTX) and CBZ on hippocampal basal, Ca(2+)- and K(+)-evoked serotonin releases, using microdialysis in freely moving rats. Basal release was reduced by TTX, GVIA and IVA (GVIA>IVA). Ca(2+)-evoked release was reduced by GVIA but unaffected by TTX and IVA. K(+)-evoked release was reduced by TTX, GVIA and IVA (GVIA+info)