Central adenosine receptors: possible involvement in the chronic effects of caffeine.
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Biomedical subjects
Publications and source records attributed to R M Post.
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Acute and prophylactic effects of carbamazepine are documented in a double-blind clinical trial in a 55-year-old treatment-refractory, lithium-non-responsive, manic-depressive patient. Double-blind crossover to two other anticonvulsants was also achieved; the patient showed no evidence of response to phenytoin or valproic acid. The clinical and theoretical issues raised by the selective response to carbamazepine in this patient are discussed.
Lithium carbonate appears to inhibit the development of cocaine-induced behavioral sensitization while it does not inhibit the development of amygdala kindling. Lithium chloride did not inhibit kindled seizures. Carbamazepine does not inhibit cocaine-induced motor activity or the development of behavioral sensitization in the rat. Carbamazepine is highly effective in blocking completed amygdala-kindled seizures, but does not block their development in the rat. Lithium carbonate and carbamazepine, two drugs of use in the prophylactic treatment of affective illness, appear to have differential effects on sensitization and kindling.
It has been generally accepted that increased thyroid function facilitates treatment response in depression. Recent data show that response to several antidepressant treatments, particularly lithium and carbamazepine, are associated with decreased thyroid hormone levels. An alternative hypothesis that decreased thyroid indices are related to antidepressant response is proposed and clinical and research implications are discussed.
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An oral contraceptive was used successfully to treat recurrent premenstrual depressions and a subsequent major depressive episode in a 20-year-old woman. The relationship between premenstrual and major depressions is explored and the overlapping CNS effects of gonadal steroids and classical antidepressants are discussed.
Multiple personality disorder (MPD) should be considered in cases where there have been multiple diagnoses, failure of conventional treatments, a mixture of psychiatric and somatic symptoms, and/or extremely rapid shifts in symptoms and level of function. Proper diagnosis and treatment often leads to a significant amelioration in symptoms and increase in level of function for a patient previously refractory to treatment.
Carbamazepine, a drug effective in pain, seizure, and affective disorders, was screened for its ability to interact with a variety of neurotransmitter and neuromodulator binding sites on brain membranes. The most potent effect was observed on adenosine antagonist ( [3H]DPX) binding to the adenosine receptor (KI = 3.5 +/- 0.4 microM) followed by adenosine agonist ( [3H]CHA) binding (KI = 24.5 +/- 3.6 microM). Lower potency effects were observed on benzodiazepine receptors, and no inhibition was seen in a variety of other systems. The inhibition of adenosine receptor binding by carbamazepine was competitive. No correlation was observed between the potency of a series of carbamazepine analogs as inhibitors of either ( [3H]DPX, [3H]CHA or [3H]diazepam binding and their ability to inhibit electroshock-induced convulsions, suggesting that the anticonvulsant properties of these agents are not mediated by the adenosine receptor, but raising the possibility that other clinical effects of carbamazepine may relate to its ability to act at the adenosine receptor.
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Caffeine, a potent central stimulant, is known to competitively inhibit the specific binding of both adenosine and benzodiazepine receptor ligands to brain membranes in vitro. In mice receiving a diet containing non-toxic doses of caffeine (200 or 400 mg/kg diet) for periods up to 40 days, a dose-related increase in the number of binding sites for [3H]-CHA and [3H] DPX was observed in whole brain membranes without modifications of the receptors' affinity. Furthermore, a transitory increase in the number of [3H]-DZP binding sites was observed. These preliminary data seem to confirm the involvement of the adenosine receptors in the mode of action of caffeine and may be relevant to the development of both tolerance and dependence to some of the central effects of this compound.
Somatostatin is a hypothalamic tetradecapeptide with many actions. We investigated a potential role for somatostatinergic neuron dysfunction in affective disorder by measuring somatostatin in the CSF of 47 patients with affective illness and of 39 normal volunteers. Medication-free depressed patients showed significantly lower levels of CSF somatostatin than normal volunteers (P less than .001) or patients during the improved state (P less than .01). A significant inverse correlation was observed between somatostatin and the duration of sleep on the night of the lumbar puncture. We also observed significant correlations between somatostatin and 5-hydroxyindoleacetic acid and norepinephrine in the CSF. Also noted were the significance of depression-related decreases in CSF somatostatin in relation to information about central somatostatin secretion, reported abnormalities of somatostatin activity, and potential interactions between alterations in somatostatin activity and the pathophysiology of depression.
Computed tomographic (CT) scans of 28 chronic schizophrenic patients, 15 chronic schizoaffective patients, and 19 patients with bipolar affective disorder were compared on three measures: ventricular size, sulcal prominence (cortical atrophy), and cerebellar atrophy. Because the patients with bipolar disorder were older, measures were adjusted by controlling for age statistically or excluding patients over age 50 years. After age correction, there were no significant differences across diagnostic groups. Each group contained some subjects with enlarged ventricles, sulcal prominence, and/or cerebellar atrophy. The similarity of CT scan results across the three groups argues against ascribing these abnormalities to any one psychiatric disorder or to a specific drug effect. Sampling effects and the possibility of differential causes of the findings in the different diagnostic groups must be considered. Examination of the correlations of these three CT scan measures found them to be significantly related to each other. Age correlated with all measures when patients over age 50 years were included in the analysis, but not for patients aged 50 years and younger.