Stability-indicating methods for determination of pyritinol dihydrochloride in the presence of its precursor and degradation product by derivative spectrophotometry.

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvent. Linear relationships were obtained in the ranges of 6-22 microg/mL for the (1D) method and 6-20 microg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 +/- 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 +/- 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of < or = 10% (II) and < or = 50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.

Treatment of the organic brain syndrome in the elderly. A double-blind comparison on the effects of a neurotropic drug and placebo.

100 inpatients of both sexes, most of them older than 65 years and suffering from symptoms of the organic brain syndrome (OBS), primarily associated with aging were included in a 6-week double-blind study. Patients were randomly assigned to two treatment groups of 50 patients each and received either a neurotropic drug (3 X 200 mg EMD 21657) or placebo coated tablets of identical appearance. Patients were evaluated at the beginning of the study and after 6 weeks of treatment using a physician's symptom rating, the Nurses' Observation Scale for Inpatient Evaluation ( NOSIE ), EEG, and a psychometric test battery to assess level of mental and memory functioning ( Rey test, Benton visual retention test, block design test by Kohs ). At the final assessment global response and overall tolerance were rated by the physician. The therapeutic effects of EMD 21657 were shown to be statistically significant compared to placebo in global response (p less than or equal to 0.05), in the factor 'cognitive disturbances' (p less than or equal to 0.05 doctor's symptom rating) and in the negative factors of the NOSIE (p less than or equal to 0.05). In the other parameters of the scales, the EEG and the mental ability tests no statistically significant changes could be demonstrated in the two groups after 6 weeks of treatment. The drugs were well tolerated. EMD 21657 treatment was interrupted because of side effects (increased aggressiveness, rash) in 2 cases.

JPC-80, a new slow acting antirheumatoid drug.

JPC-80 has been administered to man for the first time. Twelve patients received doses up to 300 mg daily for up to 12 weeks. Three suffered significant, but not serious, side effects: 1 skin rash, 1 elevation of liver enzymes, 1 diarrhea. All signs or symptoms returned to normal on discontinuation of drug. Four of 8 patients receiving cumulative doses of over 20 g showed moderate or major improvement. In patients with clinical improvements the mean erythrocyte sedimentation rate fell from 51 to 21, and rheumatoid factor titers fell from 1444 to 647. This pilot study justifies additional controlled studies.

Interaction of changes in hospital environment and neurotropic co-medication in chronic psychiatric inpatient. A placebo controlled double-blind study.

Chronic psychiatric patients (N = 42) predominantly diagnosed as schizophrenics, who had been hospitalized for the mean of 9 years were treated in a double-blind study with a neurotropic drug (tamitinol dihydrochloride coated tablets of 300 mg t.i.d.) and placebo. Test drugs were administered concomitantly to the existing drug therapy during two treatment periods of 6 weeks each with an interval of two months free of test medication. In the second treatment period patients moved to a new building. It was expected that neurotropic drug effects can be made clearer after the transfer requiring patient's reorientation in a new environment than before the transfer. Assessment of efficacy was made using observer ratings (Psychic and Somatic Findings of the A.M.P. System, WING Behaviour Rating Scale) and patient's self ratings (Adjective Check List. List of Somatic Symptoms) and clinical laboratory parameters. Results show that neurotropic co-medication reduced the "neurological syndrome" and the "psychoorganic syndrome" (A.M.P. System). An amelioration of the "neurological syndrome" was observed at the end of the first and at the end of the second medication phase (p less than or equal to 0.10) whilst the improvement of the "psychoorganic syndrome" was particularly evident as expected after the transfer to the new building (p less than or equal to 0.001) Patients receiving placebo described themselves as more active than patients receiving the test drug. (Adjective Check List: p less than or equal to 0.10). No subjective or objective side effects (List of somatic symptoms and laboratory parameters) were evident due to the test medication which was tolerated by all patients.

Tamitinol in paedopsychiatric out-patient therapy.

A study was carried out in 11 children, ranging in age from 7 to 12 years, to determine the clinical effect of tamitinol, in addition to psychotherapy, in alleviating disturbances of learning and behaviour. Tamitinol was administered as one 100 mg tablet per 10 kg body weight daily for 8 weeks. Assessments were made of the patients' mental condition using a 7-point rating scale, before and during treatment. Global response to treatment and tolerance were evaluated at the end of the trial by the clinician and the patients (or parents). Significant improvement was noted in 7 of the 10 children who completed the study. Six of the 13 psychiatric symptoms evaluated by the clinician were significantly improved (p less than 0.01). The drug was well tolerated by all patients.

Neurotropic drugs as co-medication to psychotropics. Combined administration of a neurotropic drug and a tetracyclic antidepressant.

Interactions of EMD 21 657 - a neurotropic drug - and maprotiline were studied in 40 depressive outpatients. Patients were assigned at random to an experimental or a control group. 20 patients of the experimental group received EMD 21 657 (3 X 400 mg/day p.o.) in addition to maprotiline (75 mg/day p.o.) during an initial treatment of 10 days. 20 patients of the control group were treated during this period with maprotiline of the same dosage but did not received EMD 21 657 as co-medication. During the 10-day period of treatment and observation, subjective information on the first day of improvement of depressive symptoms and severity of side effects were recorded. Under supplementary treatment with EMD 21 657 the onset of antidepressant action occurred sooner than in the control group receiving maprotiline alone. The earlier improvement in the experimental group was statistically significant in the target symptom 'obsessive rumination' (p less than 0.01). Undesirable effects of maprotiline treatment were seldom observed or were mild in terms of severity. A decrease in the rate of side effects in the experimental group could not be shown statistically.

Treatment of the alcoholic organic brain syndrome with EMD 21657. A derivative of a pyritinolmetabolite: double-blind clinical, quantitative EEG and psychometric studies.

The efficacy of EMD 21657--a derivative of a pyritinolmetabolite--with regard to the improvement of the organic brain syndrome (OBS) of chronic alcoholics was investigated in a double-blind study utilizing clinical, psychometric and quantitative EEG evaluation. Nineteen patients received 3 x 300 mg EMD and 21 patients 3 x 1 dragee placebo for 6 weeks. The groups did not differ in regard to age, sex, weight, height, alcohol anamnesis or IQ. The hospitalized patients were examined before as well as at the end of the second, fourth and sixth week of drug treatment. While the overall evaluation by the psychiatrist and patients at the end of the period of treatment did not show marked intergroup differences, the clinical global impression scale and the OBS rating scale demonstrated that both groups showed a significant reduction in their OBS and that improvement with EMD 21657 therapy was significantly superior to the one with placebo. Psychometric analysis also exhibited a significant superiority of EMD in regard to the general, associative, numeric and total verbal memory, concentration and attention variability. Psychovisual memory and the quantative aspects of attention showed opposite findings. Flickerlight fusion frequency, reaction time and after-image did not change significantly. The psychomotor activity improved significantly more with EMD than placebo; this was especially pronounced in the left hand. Affect and mood improved also more with EMD than placebo. Side effects were observed more frequently under active treatment and were characterized by temporary headaches. Power spectral density analysis of the EEG revealed in both groups a decrease of delta, fast alpha and beta activities and an increase in theta and slow alpha activity, but changes during EMD treatment more frequently reached the level of statistical significance than with placebo. The most consistant finding was the theta augmentation under EMD treatment. It was concluded that EMD 21657 is a CNS-effective drug with pronounced nootropic and slight thymotropic properties.

Accelerated remission of the alcoholic organic brain syndrome with EMD 21657. Double-blind clinical and psychometric trials.

The efficacy of EMD 21657--a derivative of a pyritinol metabolite--on the alcoholic orangic brain syndrome (OBS)) was investigated in a double-blind placebo-controlled study. 19 patients received 3X300 mg EMD, 21 patients 3X1 dragée placebo throughout 6 weeks. The two groups did not differ as to age, sex, weight, height, alcohol anamnesis and IQ. Investigations were carried out before and at the end of the 2nd, 4th and 6th weeks of drug treatment. While an overall evaluation by doctor and patient at the end of the therapy did not reveal any signficant differences, it was found by means of the global score and OBS score that the OBS improved under both substances, but significantly more so with EMD. Psychometric analysis demonstrated that EMD was superior to placebo in regard to general, associative and numeric memory, concentration and attention variability, psychomotor activity, affect and mood, while the Benton test and attention showed opposite findings. Side effects were observed more under EMD than placebo therapy and consisted of temporary headaches and dizziness. Our findings demonstrated that EMD 21657 has pronounced nootropic and some thymotropic effects.

[Characteristics of the antivitamin effect of pyriditol, a disulfide pyridoxine derivative, on animal body]. / Kharakteristika antivitaminnogo deistviia disul'fidnogo proizvodnogo piridoksina-piriditola-na zhivotnyi organizm

Intraperitoneal administration of disulphide pyridoxine (pyriditol) to albino mice in a dose of 300 mg/kg brings down the GABA level and the GABA-transaminase activity in the brain, the glutamic acid content and the glutamate-decarboxylase activity remaining unchanged. In the liver and, especially, in the kidneys of test animals the activity of aspartate-and alanine-aminotransferase goes down. The diurnal urinary output of the animals shows a decreased passage of 4-pyridoxic acid. These results are interpreted to be consequent upon the antivitamin action of pyriditol with respect to pyridoxine.