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The influence of biperiden in overdose on respiration and circulation in the dog.

Biperiden lactate was administered intravenously in overdose to dogs under general anaesthesia. Biperiden appeared to have a toxic influence on respiration and circulation independently. Respiratory arrest occurred at a dose of 33 +/- 10 mg/kg and has probably a central origin. When artificial ventilation was instituted circulatory standstill occurred at a dose of 45 +/- 5 mg/kg. The toxic influence of biperiden is characterised by a decrease of heart rate and of left ventricular contractility resulting in cardiogenic shock. Biperiden is compared with orphenadrine as far as its potential hazard is concerned for patients trying to commit suicide by ingesting an overdose.

Animals

Differential antagonism of antiavoidance, cataleptic and ptotic effects of neuroleptics by biperiden.

The interaction between neuroleptics and an anticholinergic, biperiden, in the antiavoidance, catalepsy and ptosis tests was investigated in mice for the purpose of predicting the extrapyramidal side-effects of neuroleptics. The cataleptic effect of most neuroleptics used was antagonized to some extent by biperiden, while the ptotic effect was hardly influenced. The antiavoidance effect of haloperidol, trifluperidol and perphenazine was markedly antagonized and that of chlorpromazine moderately. However, the effect of thioridazine, chlorprothixene, levomepromazine and clozapine was little antagonized. In neuropharmacological tests, haloperidol, trifluperidol and perphenazine exhibited a selective antidopaminergic activity, while chlorprothixene, levomepromazine and clozapine showed antidopaminergic, antiadrenergic and also anticholinergic activities when similar doses were given. These results indicate that biperiden antagonism may be marked in the tests related to the extrapyramidal symptoms and in drugs liable to induce extrapyramidal side effects, however, there would be little or no antagonism in drugs possessing the anticholinergic property and eliciting few extrapyramidal side-effects.

Animals

[Central and peripheral interactions of the antiparkinson agent biperiden and the antihistaminic bamipin on the rat excited by pilocarpine].

Excitatory reactions elicited by pilocarpine HCl (50 mg/kg i.v. in 6 s) are used for demonstrating synergistic effects of the central anticholinergic drug biperiden (Akineton) and the antihistamine bamipine (Soventol). Scratching movements of the hind legs are used as parameter for central activity, salivation for peripheral and death for toxic drug effect, respectively. The results show distinct synergistic (central) activity of drug combinations concerning the inhibition of scratching movements. On the contrary, no intensified inhibition is found with the peripheal symptom salivation bamipine rather induces an attenuation of inhibitory effects seen after hig doses of biperiden. Furthermore, the enhanced toxicity of pilocarpine caused by bamipine in a defined dosage range is antagonized by biperiden in a dose related manner. The results of the animal experiments presented are paralleled with clinical experience.

Animals

[Neuropsychological investigations on short-time effects of biperiden (Akineton) in Parkinson's Disease (author's transl)].

In 10 parkinsonian patients the short-time effects of biperiden after slow, intravenous application were investigated in comparison with a placebo group. Immediately after infusion the patients, who were examined at fixed intervals using standardized tests of psychomotor function, mood, and affect, showed a marked impairment os psychomotor function and reaction time, which in time did not exceed the placebo effects. Simultaneously there could be demonstrated an increasing affective stimulation with an acceleration of operating time and improvement of mood. These findings demonstrate- analogously to the intravenous application of L-Dopa-a psychotropic effect independent of the eventual antiakinetic properties of biperiden. The frequency of exogenous psychotic reactions in patients with marked psychoorganic alteration restricts the applicability of anticholinergic drugs in the treatment of an akinetic crisis.

Affect

[Treatment of acute schizophrenic stupor: the effect of biperiden (author's transl)].

The study reports about the intravenous application of Biperiden at patients with acute hypokinetic reaction suffering from schizophrenia of the paranoid-hallucinatory type. In all of the six cases examined a fast abolition of the stupor could be observed. The pathophysiological mechanisms deriving from our clinical experiences are discussed. Furthermore, a therapeutic procedure is suggested to treat acute schizophrenic stupor merely with drugs.

Acute Disease

[Treatment of the neuroleptic syndrome by biperiden hydrochloride under its delayed-action form. A 9-month study on 55 hospitalized patients].

Biperiden hydrochloride has been used in the treatment of Parkinson's disease and related disorders within two drugs: --Akinophyl, --and Akineton which is chemically similar but has a slower effect. The first French publications upon its use as a neuroleptic corrector date from 1972. Our study deals with 55 chronic psychotic patients treated with neuroleptics and varied correctors of resulting Parkinson disorders. Akineton has been substituted for the preceding antiparkinson drugs. We may come to the following conclusions = Akineton is effective upon neuroleptic syndrom, gives few or no untoward reactions, has no toxicologic effects, shows no incompatibility with any other drug. It is very satisfactory to have at our disposal a drug effective in small doses and having a slow effect within average of 24 hours.

Adult

The movement pattern of oral tardive dyskinesia in relation to anticholinergic and antidopaminergic treatment.

24 hospitalized psychiatric patients with neuroleptic-induced tardive dyskinesia were treated with alpha-methyl-para-tyrosine (AMPT), 4 g daily for 3 days, and biperiden, 12 mg daily for 3 weeks. The results were evaluated blindly by means of videotape technique. The frequency of tardive dyskinesia was significantly reduced by AMPT and significantly increased by biperiden. The amplitude was reduced by AMPT in ten cases, unchanged in 12 cases and increased in two cases. Biperiden significantly increased the amplitude. The duration of each separate tongue protrusion and/or mouth opening was significantly increased by AMPT and reduced or unchanged by biperiden. It is concluded that a reduced dopaminergic activity (pharmacological or organic) may constitute the primary pathogenetic background for tardive dyskinesia, but that dopaminergic hypersensitivity and/or cholinergic hypofunction is necessary before the hyperkinetic element of the movement disturbances can minifest itself.

Adult

Distinguishing acute and tardive akathisia by monitoring microvibration: a pilot study.

One acute and one tardive akathisia patients, respectively, and 10 neuroleptic-treated schizophrenic patients were injected with biperiden 5 mg or saline and the response to anticholinergics was monitored by microvibration (MV) as an indicator of muscle tonus. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The biperiden injection markedly reduced the power spectral values of MV in acute akathisia. In contrast with acute akathisia, the biperiden injection significantly increased the power spectral values of MV in tardive akathisia. The subjective feelings of akathisia patients were parallel to the power spectral values of MV. Control patients were not affected by such treatment. The present findings show that the subjective symptoms of akathisia can be well defined by the objective, differential response to anticholinergics in a manner similar to the visible extrapyramidal symptoms (dystonia, dyskinesia) induced by neuroleptics.

Acute Disease

[Involvement of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans].

In an attempt to elucidate the role of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans, we examined 17 healthy male volunteers for ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia on three separate days in a randomized, double-blind fashion. Pirenzepine, a M1 muscarinic antagonist which does not cross the blood-brain barrier, biperiden, another M1 muscarinic antagonist which is expected to penetrate into the central nervous system, or placebo was intravenously preinjected before the measurement of ventilatory responses. There were no significant differences in the mean magnitude of ventilatory responses among the three experimental days. However, despite the poor correlation between the magnitude of ventilatory response to hypercapnia in the placebo and pirenzepine studies, there was a significant correlation between them when the value in the pirenzepine study was expressed as % of control, value i.e., subjects with greater hypercapnic ventilatory response in the placebo study showed greater declines with biperiden. Since these relations were seen only for the ventilatory response to hypercapnia with biperiden, we suggest that a cholinergic mechanism, particularly the M1 muscarinic receptor, may be involved in chemoreception to CO2 in the central nervous system and constitute the neurochemical background for the interindividual variation in hypercapnic ventilatory response in humans.

Adolescent

Respiratory dyskinesia: a variety of clinical forms differentially diagnosed by using a spirograph.

Four cases of respiratory dyskinesia were investigated by using a spirograph before and after biperiden injection. The abnormal respiratory patterns in four cases appeared to be in two types and these abnormalities were abolished after biperiden injection. The present study showed that respiratory dyskinesia could be defined more clearly by using a spirograph and these results are useful for the diagnosis of patients with respiratory discomfort while undergoing neuroleptic drug treatment.

Adult

A case of tardive Tourette-like syndrome.

We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.

Adult