Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurones and astrocytes.

A preferential effect of valproate on gamma-aminobutyric acid (GABA) in the nerve terminal compartment has been proposed. Gamma-vinyl GABA, an irreversible inhibitor of GABA-transaminase (GABA-T) causes a preferential increase in the GABA compartment of the non-nerve terminal. The aim of the present study was to investigate further this apparent differential effect on GABA-T of these compounds in neurones and glia.

Afternoon cortisol levels before (spontaneous) and after suppression with dexamethasone or oxazepam in depressed patients.

In 35 hospitalized depressed patients afternoon plasma cortisol (15:00-15:20 h) was measured in 3 ways: spontaneous, 2 h after administration of 45 mg oxazepam, and 16 h after administration of 2 mg dexamethasone. Dexamethasone and oxazepam caused a marked suppression of cortisol secretion, the former being the most pronounced. A significant correlation between spontaneous and suppressed cortisol levels was found and a correlation between the suppressed cortisol levels was also demonstrated.

Steady-state levels of imipramine and its metabolites: significance of dose-dependent kinetics.

Seventeen hospitalized patients (age 39-66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d.

Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism.

Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.

Benzodiazepine suppression of cortisol secretion: a measure of anxiolytic activity?

Clinical studies on spontaneous afternoon cortisol levels in depressed patients revealed that oxazepam given a few hours before blood sampling, may suppress the cortisol levels. This was confirmed in a volunteer study, where oxazepam 30 and 60 mg caused a dose-dependent suppression of the cortisol level only lasting 2 or 3 hours in spite of persisting high oxazepam levels in plasma. Subsequently, a study in 28 depressed patients showed a substantial suppression of afternoon cortisol after oxazepam 45 mg given 2 hrs prior to sampling.

Sparteine oxidation polymorphism in Denmark.

Sparteine oxidation was polymorphic among 301 healthy Danish volunteers. Hence 22 subjects or 7.3% were phenotyped as poor metabolizers (PM) whereas 279 subjects were classified as extensive metabolizers (EM).

Long-term study of gamma-vinyl GABA in the treatment of epilepsy.

The purpose of this study was to investigate the long-term efficacy and tolerability of gamma-vinyl GABA (GVG) in the treatment of epilepsy. 36 patients with severe therapy resistant epilepsies participated, the majority exhibiting complex partial seizures. The mean follow-up period was 9.

Valproate: an updated review.

Valproate in all its aspects is comprehensively surveyed. Previous reviews covering various aspects such as mechanism of action, clinical pharmacology, clinical efficacy in epilepsy, febrile convulsions and other neurological disorders, side effects, teratogenicity and intoxications are discussed and updated (161 references).

Spontaneous afternoon plasma cortisol in depression.

Spontaneous plasma cortisol was measured in the interval from 15.00-18.00 h 74 hospitalized depressed patients (56 endogenously and 18 non-endogenously depressed according to the Newcastle index).

Microcalorimetry as a Rapid Method for Estimation of Bacterial Levels in Ground Meat.

The potential of microcalorimetry as a rapid method for the estimation of bacterial levels in ground meat was studied. The exothermic heat production rates (HPRs) of Escherichia coli and meat suspensions were measured in a BioActivity Monitor and correlated to log CFU/ml or g. Comparative experiments using 0.

gamma-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy.

The antiepileptic effect of gamma-vinyl gamma-aminobutyric acid (GABA), an irreversible GABA-transaminase inhibitor, was investigated in an add-on, placebo-controlled, double-blind, cross-over, fixed-dose trial. Twenty-one patients suffering from difficult to control complex partial seizures participated; 18 patients completed the trial. Serum levels of concomitant antiepileptic drugs were kept constant throughout the trial.

Dextropropoxyphene kinetics after single and repeated oral doses in man.

The kinetics of dextropropoxyphene (DP) and its main metabolite norpropoxyphene (NP) were studied in 6 healthy male subjects after a single oral dose of 195 mg DP HCl, and during and after 12 daily single oral doses of 195 mg DP HCl. The kinetics varied up to five-fold between individuals after the single dose, the apparent mean elimination half-life (t1/2) was 16 h for DP and 29 h for NP. The mean apparent overall plasma clearance (CL) for DP was 2.

Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients.

Thirteen elderly depressed patients (age 60-82 years) were treated for 5 weeks with a fixed dose of amitriptyline 100 mg (sustained release preparation). In all patients the sum of concentrations of amitriptyline and nortriptyline exceeded 130 micrograms/l, which is the recommended plasma level. Cardiovascular side effects were recorded by monitoring heart rate, blood pressure, standard ECG and systolic time intervals.

Mianserin protein binding in serum and plasma from healthy subjects and patients with depression and rheumatoid arthritis.

Mianserin protein binding was measured in serum from 43 healthy subjects and plasma from 12 elderly depressed patients and 23 patients with rheumatoid arthritis. Free fraction (mean +/- SD) was 5.5 +/- 0.

Orthostatic side effects of clomipramine and citalopram during treatment for depression.

Orthostatic hypotension, the clinically most important side effect in treatment with tricyclic antidepressants, was investigated in a double-blind study with clomipramine and the selective serotonin reuptake inhibitor citalopram given for 5 weeks. All patients were initially given placebo for 1 week. In the clomipramine group (n = 17) a significant orthostatic drop in the systolic blood pressure was observed during treatment; this remained significant over the whole investigational period.

Zuclopenthixol decanoate in schizophrenia: serum levels and clinical state.

Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration.

Weight gain during treatment with valproate.

An analysis was made of weight changes during treatment with valproate in 63 adult epileptic patients. 36 patients (57%) gained more than 4 kg in weight during treatment, while 27 patients (43%) were stable in weight with weight changes of less than +/- 4 kg. There were no significant differences between weight gainers and weight-stable patients with regard to age, sex, pretreatment overweight, duration of treatment, dosage or serum levels of valproate.

Sympathetic hyperreactivity in offspring of essential hypertensive patients.

A multistage exercise test was carried out in normotensive subjects with normotensive parents (controls; n = 12), and 32 offspring of essential hypertensive patients that were normotensive (NTO; n = 20) or borderline hypertensive (BHO; n = 12) The groups were comparable as to age, weight and working capacity. Changes in sympathetic nervous activity were determined by measurements of plasma noradrenaline. The initial rise in noradrenaline levels during the exercise test was proportional to the increase in work load until the noradrenaline concentration rose sharply to levels more than 1000 pg/ml above baseline levels.

Imipramine treatment of painful diabetic neuropathy.

Twelve patients with severe, painful diabetic neuropathy in the lower extremities were treated with imipramine and placebo in a fixed-dose, double-blind, crossover study of five plus five weeks. Seven patients experienced notable improvement while receiving imipramine and none while receiving placebo. The rating of specific symptoms at the end of each treatment period showed a beneficial effect of imipramine on pain, paresthesia, dysesthesia, numbness, and nocturnal aggravation.

The effects of carbamazepine and valproate on folate metabolism in man.

The effect of carbamazepine and valproate treatment on folate metabolism was studied in 11 epileptic patients. The absorption of folic acid and of Pteroyl-gamma-L-glutamyl-gamma-L-glutamyl-L-glutamic acid, a synthetic substrate for intestinal folate deconjugase , was measured prior to and after 2 months of antiepileptic therapy with either carbamazepine (5 cases) or valproate (6 cases). After 2 months' treatment, the area under plasma concentration versus time curve was significantly decreased and t-max (time when maximal plasma concentration is obtained) was significantly prolonged.

Suppression of plasma cortisol after oral administration of oxazepam in man.

In seven healthy male subjects plasma cortisol was measured at 20 min intervals from 07.00 to 13.00 h, during a drug free control test and after oral administration of 30 and 60 mg oxazepam.

D-propoxyphene kinetics in man: significance of a deep third compartment.

Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model.

Assessment of symptom change from improvement curves on the Hamilton depression scale in trials with antidepressants.

A total of 97 patients, who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine, were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale (HDS). Although we confirmed that our six-item HDS subscale, in contrast to the total 17-item HDS, was a one-dimensional measure of depression, the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient, i.e.