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.     

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.     

Assessment of blood flow velocity during cognitive stimulation in persons with suspected hydrocephalus

The aim of this work is to evaluate middle cerebral arteries (MCA) blood flow velocity changes during performance of linguistic and visuospatial cognitive tasks. Two groups were investigated: eight patients with suspected hydrocephalus without perceptible cognitive disturbances, and eight healthy persons. Blood flow velocity in left and right MCA was recorded with transcranial Doppler sonography while the examined patients were performing three different tasks. The analysis of the results showed differences between the groups concerning both increase of blood flow velocity values and performance patterns. Compared to healthy individuals less increase in blood flow velocity during performance of all tasks and no difference in haemodynamic changes between both hemispheres during task performance were observed in patients with hydrocephalus. The results obtained suggest, that the pattern of functional lateralization in brain in patients with suspected hydrocephalus is probably changed.     

Posttraumatic ectopic calcification as an additional pathologic factor of brachial plexus palsy

The authors describe a case of a 54-year-old male, who was attacked with a broken bottle and wounded in left supraclavicular region. No neurologic deficit was observed immediately after injury. Some days later signs of upper trunk brachial plexus palsy were detected. Gradually symptoms of the Erb syndrome have developed. He was operated on 5 months after injury. During surgery no discontinuity of the brachial plexus was found. Unexpectedly there were an inner scar and free bony fragment compressing the upper trunk and the suprascapular nerve. Both the scar and bony fragment were carefully dissected and removed. Result of surgery: pain relief, restoration of normal sensation and partial restoration of biceps function.