Application of arylosulfonic acids in analysis of antidepressive drugs

Suitability of three phenylsulphonyloxybenzenesulfonic acids and their sodium salts to form new derivatives with antidepressive drugs were studied. Then physicochemical properties of the obtained arylosulfonates were tested. Reagents mentioned above were also used in analysis of these drugs.     

Derivates of 1,1-dioxo-1,4,2-benzoditiazines. Part XII. Synthesis and pharmacology of some 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2-benzodithiazines

Preparation of some novel 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2-benzodithiazines (I-V) and its sodium salts (Ia, IVa) have been elaborated. Their chemical structures have been confirmed by elemental analysis, IR and 1H-NMR spectrometry. In preliminary pharmacological examination compounds I, Ia, IV and IVa exhibited low acute toxicity, moreover investigated compounds shown hypertensive and cholagogic activity (I, Ia) and also hypotensive (IV, IVa) or diuretic (Ia, IVa) activity, on the other hand above mentioned compounds didn't exhibit antiarrhythmic activity. Some relationships between the chemical structure and pharmacological activity of the investigated compounds have also been discussed.     

The central action of pizotifen

The central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activity was found in the despair test in rats.On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED₅₀=0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+tranylcypromine) in rats (ED₅₀=0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED₅₀=0.35 mg/kg, i.p.), and in doses of 5–10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1–0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.     

Clonidine-induced locomotor hyperactivity in rats

Summary The -adrenergic agonist, clonidine, causes sedation in normal rats. The present study demonstrates that clonidine evokes strong locomotor stimulation in rats pretreated with 6-hydroxydopamine plus reserpine. Similar, but less intensive hyperactivity is observed in rats given clonidine after combined pretreatment with 6-hydroxydopamine plus p-chlorophenylalanine plus -methyl-p-tyrosine, or with reserpine plus low doses of yohimbine. The -adrenolytic drugs, phenoxybenzamine, phentolamine and aceperone, as well as high doses of yohimbine, antagonise the clonidine-induced locomotor stimulation; in contrast, the dopamine receptor blocking agents, pimozide and spiroperidol, exert no antagonistic effect. The results indicate that in the brain of normal animals, clonidine predominantly activates presynaptic -adrenoceptors on noradrenergic neurones and thereby induces sedation. After destruction of the noradrenergic fibres by 6-hydroxydopamine plus reserpine, activation of postsynaptic -adrenoceptors prevails so that hyperactivity results.This study was supported by Polish Academy of Sciences (10.4). Preliminary accounts were presented at the Pharmacology Meeting, Hannover, September 14–17, 1976 and at the 1 st Joint Symposium of Hungarian and Polish Pharmacological Societies, Zakopane, October, 13–15, 1976     

Kniegelenksmeniskusverletzungen im Kindesalter mit Berücksichtigung der Nachuntersuchungen

Zusammenfassung Es wurden 30 Fälle der Kniegelenksmeniskusverletzung im Kindesalter vorgestellt, die operativ behandelt waren. 20 der Behandelten wurden nach 1–12 Jahren nach dem operativen Eingriff nachuntersucht. Es wurden n die Ätiologie, der Verletzungsmechanismus und der klinische Befund besprochen. Die klinische und radiologische Nachuntersuchung ermöglichte die morphologische und funktionelle Auswertung des Kniegelenks nach der Meniskusverletzung.

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Injury of the semilunar cartilages of the knee-joint in childhood

Summary In the paper, 30 patients at the age of 5 till 14 with injuries of the semilunar cartilages of the knee-joint, are presented. All the children were subjected to surgery, and 20 of them underwent same examinations performed in a delay of 1 to 12 years after they had been operated. Both etiology and the injury mechanism subjects are hadled together with the clinical pictures, specific to the age of the young patients. Basing on the clinical and X-ray examinations, the state of the morphological and functional condition of the knee of a child after semilunar cartilage had been removed, was considered and estimated.

     

Control of the RIA method as viewed from the standpoint of the investigation on the kinetics of the insulin-125I-antibody reaction

In this paper attempts were made towards the optimalization and the control of some parameters of the RIA reaction.Basing on the law mass action, as well as on the Scatchard's and Sips's equations, the equilibrium constants for the reversible reaction: insulin-¹²⁵I-antibody for different incubation temperatures were calculated. Moreover a characteristic of the antiinsulin antibody by means of the heterogeneity coefficient was done, as well as the values of the thermodynamic function increments were calculated, which made possible to point out explicitly the optimal shape of the standard curve.     

Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies

OBJECTIVE: To determine the validity of a clinical diagnosis of probable or possible dementia with Lewy bodies (DLB) made using International Consensus criteria. BACKGROUND: Validation studies based on retrospective chart reviews of autopsy-confirmed cases have suggested that diagnostic specificity for DLB is acceptable but case detection rates as low as 0.22 have been suggested. METHODS: We evaluated the first 50 cases reaching neuropathologic autopsy in a cohort to which Consensus clinical diagnostic criteria for DLB, National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for vascular dementia (VaD) had been prospectively applied. RESULTS: Twenty-six clinical diagnoses of DLB, 19 of AD, and 5 of VaD were made. At autopsy, 29 DLB cases, 15 AD, 5 VaD, and 1 progressive supranuclear palsy were identified. The sensitivity and specificity of a clinical diagnosis of probable DLB in this sample were 0.83 and 0.95. Of the five cases receiving a false-negative diagnosis of DLB, significant fluctuation was present in four but visual hallucinations and spontaneous motor features of parkinsonism were generally absent. Thirty-one percent of the DLB cases had additional vascular pathology and in two cases this contributed to a misdiagnosis of VaD. No correlations were found between the distribution of Lewy bodies and clinical features. CONCLUSION: The Consensus criteria for DLB performed as well in this prospective study as those for AD and VaD, with a diagnostic sensitivity substantially higher than that reported by previous retrospective studies. DLB occurs in the absence of extrapyramidal features and in the presence of comorbid cerebrovascular disease. Fluctuation is an important diagnostic indicator, reliable measures of which need to be developed further.     

Effect of therapeutic drug monitoring of amitriptyline and genotyping on efficacy and safety of depression therapy

Modern pharmacotherapy is based on precise adjustment of a dosage schedule to individual requirements of patient. Therapeutic drug monitoring is a method that allows for a more effective treatment approach, especially in the case of a narrow therapeutic index of a drug. Tricyclic antidepressant drugs are characterised by narrow therapeutic index as well as relationship between serum drug concentration and side effects. It was demonstrated that interindividual variability of blood concentrations of tricyclic antidepressant drugs is related to genetic polymorphism of oxidating enzymes participating in metabolism of these drugs. The aim of the study was to estimate the impact of therapeutic drug monitoring of tricyclic antidepressant drugs as well as genotyping on efficacy and safety of endogenous depression therapy. The study included 9 patients with established diagnosis of endogenous depression. Blood serum concentrations of amitryptyline was measured by fluorescence polarisation immune assay (FPIA, Abbott system). Genotype of cytochrome P450 isoenzyme CYP2D6 was determined using PCR-RFLP method. It was demonstrated that monitoring therapy of tricyclic antidepressant drugs in combination with determination of the genotype seems to be more safe and effective. Monitoring therapy and genotyping may be less expensive than the costs of prolonged hospitalisation and risk of side effects.