Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation in human serum in vitro.
Amitriptyline (AMI) and procainamide (PA) have been reported to inhibit the activity of human plasma butyrylcholinesterase, an enzyme important in the metabolic degradation of cocaine (COC) and its ethyl analogue cocaethylene (CE). Because both AMI and PA may be used in the treatment of COC intoxication and abuse, the effect of high pharmacological concentrations of these compounds on the degradation of COC and CE in pooled human serum was studied. AMI (1.8 micromol/L) modestly inhibited the degradation of COC by 4.2% and of CE by 4.0%. PA (42.5 micromol/L) profoundly inhibited degradation of COC by 42.7% and of CE by 47.2%. In contrast, lithium carbonate (1 mmol/L, control) showed no inhibition of degradation of either COC or CE. These results suggest that AMI and PA may prolong the half-life of COC and CE in human serum. (+info)
Depressive state with anxiety in repeated cold-stressed mice in forced swimming tests.
The effects of various types of stress and drugs were studied to assess mouse performance in forced swimming tests, following characterization of SART (specific alternation of rhythm in environmental temperature) stress. Immobility time in the test decreased in mice subjected to SART, acute cold and restraint stress. No change was noted due to chronic cold stress or repeated fasting. The shortened time did not recover even 24 hr after the end of SART and chronic restraint stress. The time in SART-stressed mice finally recovered at 5-7 days. Shortening of immobility time in SART-stressed mice was inhibited by diazepam and repeated imipramine but not by lithium carbonate. In chronic restraint-stressed mice, this time was inhibited by repeated lithium carbonate but not diazepam or imipramine. SART stress would thus appear related to anxiety and depression and may be useful for detecting new types of antidepressants. (+info)
Bipolar disorder in old age.
OBJECTIVE: To review the classification, clinical characteristics, and epidemiology of bipolar disorders in old age with a special focus on neurologic comorbidity, high mortality, and management. QUALITY OF EVIDENCE: Most available data is gleaned from retrospective chart reviews and cohort studies. Treatment recommendations are based on evidence from younger populations and a few anecdotal case reports and series involving elderly people. MAIN MESSAGE: While relatively rare in the community setting, mania in old age frequently leads to hospitalization. It is associated with late-onset neurologic disorders (especially cerebrovascular disease) involving the right hemisphere and orbitofrontal cortex. Prognosis is relatively poor; morbidity and mortality rates are high. Management of bipolarity includes cautious use of mood stabilizers, especially lithium and divalproex. CONCLUSIONS: Mania in old age should trigger a careful assessment of underlying neurologic disease, especially cerebrovascular disease. Close clinical follow up is essential. (+info)
Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat.
Although the efficacy of lithium as a mood stabilizer is well documented, the mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways that are functionally altered following long-term lithium treatment is central to elucidating a psychotherapeutic mechanism. We have used a sensitive and quantitative histochemical assay for the determination of cytochrome oxidase (CO) activity, a mitochondrial marker of neuronal activity, to determine the effect of repeated lithium treatment on regional neuronal activity in the rat brain. Oral lithium treatment (21 days) selectively decreased cytochrome oxidase activity in the cingulate cortex and regions of the nucleus accumbens. These decreases were not seen after 5 days of lithium administration, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further suggests a role for amygdala pathways in the effects of lithium following 21 days of treatment. The implications of these data for understanding the mechanisms of action of lithium are discussed. (+info)
Asthma precipitated by cessation of lithium treatment.
We report symptomatic asthma, associated with objective and highly significant increases in both airway responsiveness and airflow limitation, presenting de novo in a male patient 6 weeks after suddenly discontinuing lithium carbonate therapy. (+info)
Naltrexone exerts a favourable effect on plasma lipids in abstinent patients with alcohol dependence.
Epidemiological studies suggest that abstinence periods in some patients with alcohol dependence may increase their cardiovascular risk via proatherogenic changes in plasma lipid levels. Because of this, drugs administered in withdrawal therapy should not exacerbate these effects. The aim of this study was to estimate the influence of naltrexone, carbamazepine, and lithium carbonate on plasma lipid levels in 160 alcohol-dependent males during withdrawal therapy. Plasma concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides (TGL) were determined every 2 weeks for 20 weeks. Pharmacotherapy (naltrexone 50 mg, carbamazepine 600-800 mg, lithium carbonate 500-1000 mg once per day or placebo) was given within the framework of a double-blind study between the fourth and twentieth weeks of the study. The results of 116 patients who maintained abstinence during the whole 20-week observation period were analysed. In patients treated with naltrexone significant decreases in TC (239 +/- 58 vs 216 +/- 52 mg/dl; P < 0.01) and TGL (125 +/- 68 vs 86 +/- 33 mg/dl; P < 0.02) concentrations after 16 weeks of pharmacotherapy were observed. In patients treated with carbamazepine, significant increases in TC (224 +/- 39 vs 243 +/- 54 mg/dl, P < 0.04) and HDL (40 +/- 10 vs 44 +/- 8 mg/dl, P < 0.01) after 16 weeks of pharmacotherapy were observed. After 16 weeks of pharmacotherapy, patients treated with naltrexone had lower mean TC (P < 0.03) and LDL-C (P < 0.01) concentrations than patients treated with carbamazepine, lower mean LDL-C levels than patients treated with lithium carbonate (149 +/- 54 vs 164 +/- 57 mg/dl, P < 0.01), and lower TGL concentrations than patients of the remaining pharmacotherapy groups. We conclude that naltrexone, by its hypolipaemic effect, could be useful for withdrawal therapy in alcoholic patients, because it may decrease the cardiovascular risk in abstinent patients with alcohol dependence by lipid mechanisms. (+info)
Effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients symptomatically stable on lithium.
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)
Early alteration in glomerular reserve in humans at genetic risk of essential hypertension: mechanisms and consequences.
Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic risk (parental family history [FH]) of hypertension (26 with positive FH [FH+], 13 with negative FH [FH-]), underwent intravenous infusion of mixed amino acids. Before and during amino acid administration, we measured glomerular filtration rate (GFR), putative second messengers of amino acids (nitric oxide [NO.] metabolites and cGMP), serum insulin and amino acid concentrations, and the FE(Li)+ as an index of renal proximal tubular reabsorption. The FH+ group had a blunted GFR rise in response to amino acids (2.43+/-8.16% versus 31.0+/-13.4% rise, P:=0.0126). The amino acid-induced change in GFR correlated (r=0.786, P:<0.01) with the change in urinary NO. metabolite excretion; a diminished rise in urinary NO. metabolite excretion in the FH+ group (P:=0.0105) suggested a biochemical mechanism for the different GFR responses between FH groups: a relative inability to convert arginine to NO. The FH+ group had a far lower initial cGMP excretion at baseline (261+/-21.1 versus 579+/-84.9 nmol. h(-1)/1.73 m(2), P:=0.001), although cGMP did not change during the amino acid infusion (P:=0.703). FH status, baseline GFR, and baseline serum insulin jointly predicted GFR response to amino acids (P:=0.0013), accounting for approximately 45% of the variance in GFR response. Decline in FE(Li)+, an inverse index of proximal tubular reabsorption, paralleled increase in GFR (r=-0.506, P:=0.01), suggesting differences in proximal tubular reabsorption during amino acids between the FH groups. GFR response to amino acid infusion was blunted in the FH+ group despite significantly higher serum concentrations of 6 amino acids (arginine, isoleucine, leucine, methionine, phenylalanine, and valine) in the FH+ group, suggesting a novel form of insulin resistance (to the amino acid-translocating action of insulin) in FH+ subjects. We conclude that blunted glomerular filtration reserve in response to amino acids is an early-penetrance phenotype seen even in still-normotensive subjects at genetic risk of hypertension and is linked to impaired formation of NO. in the kidney. Corresponding changes in GFR and fractional excretion of Li(+) suggest that altered proximal tubular reabsorption after amino acids is an early pathophysiologic mechanism. Resistance to the amino acid-translocating actions of insulin may play a role in the biological response to amino acids in this setting. This glomerular reserve phenotype may be useful in genetic studies of renal traits preceding or predisposing to hypertension. (+info)