Effect of psychotropic drugs on caudate spindle in cats.
To ascertain whether neuroleptics act on the caudate nucleus itself, the effects of these compounds as well as other centrally acting drugs were examined in relation to caudate spindle and EEG arousal responses (sciatic nerve stimulation) in gallamine-immobilized cats. Haloperidol and chlorpromazine enhanced the caudate spindle at a dose which had no effect on the EEG arousal response. On the other hand, clozapine and a higher dose of chlorpromazine enhanced the caudate spindle, but depressed the arousal response. High frequency stimulation of the sciatic nerve suppressed the caudate spindle. Pentobarbital, biperiden and diazepam, while depressing the arousal response, caused an enhancement of the caudate spindle. Imipramine at a low dose had no effect on either response, whereas at a high dose this drug enhanced the caudate spindle with concomitant depression of the arousal response. From these results, it may be concluded that the enhancing action on the caudate spindle induced by haloperidol and a low dose of chlorpromazine is due to an increase in susceptibility of the caudate nucleus itself. In addition, it is suggested that depression of the activating system is involved in an appearance of the caudate spindle. (+info)
Application of a generic physiologically based pharmacokinetic model to the estimation of xenobiotic levels in human plasma.
Estimation of xenobiotic kinetics in humans frequently relies upon extrapolation from experimental data generated in animals. In an accompanying paper, we have presented a unique, generic, physiologically based pharmacokinetic model and described its application to the prediction of rat plasma pharmacokinetics from in vitro data alone. Here we demonstrate the application of the same model, parameterized for human physiology, to the estimation of plasma pharmacokinetics in humans and report a comparative evaluation against some recently published predictive methods that involve scaling from in vivo animal data. The model was parameterized through an optimization process, using a training set of in vivo data taken from the literature, and validated using a separate test set of published in vivo data. On average, the vertical divergence of the predicted plasma concentrations from the observed data, on a semilog concentration-time plot, was 0.47 log unit. For the training set, more than 80% of the predicted values of a standardized measure of the area under the concentration-time curve were within 3-fold of the observed values; over 70% of the test set predictions were within the same margin. Furthermore, in terms of predicting human clearance for the test set, the model was found to match or exceed the performance of three published interspecies scaling methods, all of which showed a distinct bias toward overprediction. We conclude that the generic physiologically based pharmacokinetic model, as a means of integrating readily determined in vitro and/or in silico data, is potentially a powerful, cost-effective tool for predicting human xenobiotic kinetics in drug discovery and risk assessment. (+info)
The effects of baclofen and cholinergic drugs on upbeat and downbeat nystagmus.
The GABAergic drug baclofen and the cholinergic drug physostigmine were administered to patients with upbeat and downbeat nystagmus. Baclofen (orally, 5 mg three times daily) reduced nystagmus slow phase velocity and distressing oscillopsia by 25-75% in four out of five patients (two upbeat nystagmus; two downbeat nystagmus). Physostigmine (1 mg single intravenous injection) increased nystagmus in five additional patients with downbeat (1) or positional downbeat nystagmus (4) for a duration of 15-20 minutes. The different interactions of baclofen and physostigmine on neurotransmission subserving vertical vestibulo-ocular reflex could account for these effects. The response to baclofen appears to be a GABA-B-ergic effect with augmentation of the physiological inhibitory influence of the vestibulo-cerebellum on the vestibular nuclei. Similarly baclofen has an inhibitory effect on the velocity storage mechanism. Cholinergic action may cause the increment of nystagmus by physostigmine. (+info)
The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.
Polypharmacy in the treatment of schizophrenic patients in three University Centers in the Federation of Bosnia and Herzegovina (F/BH).
BACKGROUND: Polypharmacy in psychiatry is becoming the rule rather than the exception. Using more drugs at same time usually occurs where single drugs are considered insufficiently effective. SUBJECTS AND METHODS: The sample consisted of 216 patients: 85 from Sarajevo, and 44 and 87 respectively from Mostar and Tuzla. All schizophrenic patients who were hospitalised in three University Centers of F/BiH (Sarajevo, Tuzla, Mostar) on a particular day are included in the study. This included patients of both sexes (131 (60.65%) males and 85 females (39.35%)), 20-60 ages, who were on antipsychotic treatment with an established diagnosis of schizophrenia by the treating psychiatrist. The research was performed in the year 2004. The census of patients was conducted simultaneously in all three Centers, using a questionnaire in which all routine prescribed antipsychotics were registered, as the common method of the administration, and the doses as well saving as data for other medications that were simultaneously prescribed to the patients that day. RESULTS: Within the total sample the most frequently applied classical antipsychotics were haloperidol, promazine and from the group of new antipsychotics clozapine. The most frequently used other medications were biperidine and diazepam. The administration of all medication was followed through recording of individual doses, daily doses and frequency of administration. There are statistically significant differences regarding the frequency of biperidine use between the centers (p=0.008). CONCLUSION: In three University Clinical Centers of the Federation of Bosnia and Herzegovina (Sarajevo, Tuzla and Mostar), the applied rule is that more drugs in the treatment of schizophrenic psychosis and doing polypharmacy is the inevitable approach to treatment. The concept behind the polypharmacy is based on the fact that antipsychotic drugs do not cover all the symptoms of schizophrenic psychosis, and that additional medications may correct iatrogenic side effects caused by antipsychotic drugs. It is expected that the new atypical antipsychotics will treat much broader symptoms of psychosis and will not cause extrapyramidal side effects, as do the typical antipsychotics. (+info)