Anticholinergic Antiparkinson Drugs Research Articles

Usos Lícito e Ilícito dos Fármacos

Drugs of abuse are a heterogeneous group of xenobiotics or endobiotics that alter synaptic organization in the central nervous system in a transient or permanent basis, often leading to a compulsively use. What unites its members is that they confer pleasure (hedonism) to the abusers, namely by their action in the mesolimbic dopamine system. To exert its effects, different drugs of abuse will act on receptors and neurotransmitter transporters, modeling neurotransmitter release into the synaptic cleft. Besides acting on presynaptic neurons also function in neurotransmitter receptors and ion channels in postsynaptic neurons, thereby modifying the signaling pathways. In this work, the pharmacodynamic and the potential of some psychoactive substances that are typically subjected to abuse in Portugal, is reviewed. With this approach it was also possible a discussion of drugs of abuse that exhibit very different toxicological effects such as stimulants, depressants and hallucinogens. Particularly, the potential to induce dependence and addition, as well as to undergo illicit and licit uses, of central nervous system depressants, stimulants, anticholinergic antiparkinson drugs, opioids, cannabinoids and hallucinogens, is discussed.

How Psychotropic Polypharmacy in Schizophrenia Begins: A Longitudinal Perspective

While patients with schizophrenia are often treated with psychotropic polypharmacy, how and when polypharmacy begins is not well documented. A systematic chart review of 300 patients, 100 of whom were psychotropic-free prior to their first visit, was conducted to examine 2-year longitudinal prescription patterns of concomitant psychotropics, in addition to a primary antipsychotic. Overall polypharmacy occurred in 79% patients, with 2-year rates of the use of hypnotics, benzodiazepine derivative anxiolytics, anticholinergic drugs, antidepressants, and mood stabilizers were 56.7, 49.7, 38.3, 21.3, and 14.0%, respectively. Once polypharmacy had started, it was continued until their final visit in >70% of the patients. In a subgroup of 100 psychotropic-free patients, mood stabilizers, antidepressants, anticholinergic antiparkinsonian drugs, anxiolytics, and hypnotics were initiated after 2.3, 2.3, 2.1, 1.6, and 1.5 antipsychotics had been prescribed, respectively (mean duration before the introduction of a concomitant drug in days: 17.7, 121.6, 86.4, 32.1, and, 57.7, respectively). Routine practice deviates significantly from algorithms--with polypharmacy often being initiated early, often a without trial of other options, and once started commonly stays.

Anti-nicotinic properties of anticholinergic antiparkinson drugs.

The nature of the antagonism by anticholinergic compounds of nicotine-induced convulsion in mice has not been defined clearly. Although, because they do not compete effectively for agonist binding to brain tissue in-vitro, these compounds are thought to be non-competitive antagonists in the brain, pharmacological evidence is lacking. This study describes the anti-nicotinic properties of the clinically used anticholinergic antiparkinson drugs, benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl. Nicotine-induced convulsion and arecoline-induced tremor in mice were effectively prevented by these drugs. The concentrations of benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl affording 50% prevention of nicotine-induced convulsion (ED50 values) were 7.4, 4.6, 7.8, 4.9, 3.1 and 3.3 mg kg(-1), respectively. The classical muscarinic receptor antagonist atropine had potent anti-muscarinic effects but very weak anti-nicotinic activity. The classical nicotinic receptor antagonist mecamylamine had potent anti-nicotinic activity but no anti-muscarinic effects. The pattern of shift of the dose-response curve for nicotine-induced convulsion in mice was determined in the presence of increasing concentrations of the anticholinergic antiparkinson drugs. These drugs were found to increase the ED50 (0.49 mg kg(-1)) of nicotine-induced convulsion in a dose-related manner. The maximum effect of nicotine and the slope of nicotine dose-response curve were not significantly influenced by either low or high doses of benztropine, procyclidine or trihexylphenidyl, which suggests competitive action. Biperiden, caramiphen and ethopropazine, at low doses which significantly increased the ED50 of nicotine, did not affect the maximum effect of nicotine or the slope of the nicotine dose-response curve; at higher doses, however, they reduced the maximum effect and the slope, which suggests that these drugs have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice. The experiments demonstrate that the anticholinergic antiparkinson drugs and mecamylamine effectively antagonize nicotine-induced convulsion, but atropine does not; some of these drugs have competitive properties whereas others seem to have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice.

Prescription persistence and safety of antipsychotic medication: a national registry-based 3-year follow-up

Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway. Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted. The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine. Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine

Extrapyramidal side-effects induced by antipsychotic drugs are treated with dose reduction or substitution with another antipsychotic drug or by the addition of anticholinergic antiparkinson agents. The withdrawal of orphenadrine from the Norwegian market provided a possibility to investigate to what degree these alternative measures were taken in clinical practice. Data were drawn from the Norwegian Prescription Database on the sales of antipsychotics and one of the two anticholinergic antiparkinson agents marketed in 2004, orphenadrine and biperiden, to a total of 39 758 outpatients. The patients were reinvestigated in 2007. The consequences of the withdrawal of orphenadrine from the Norwegian market in 2005 regarding dosing, switching and cessation of antipsychotics and use of anticholinergics were assessed for orphenadrine users compared with biperiden users. Of the patients originally using orphenadrine, 28.4% stopped using the drug without reducing the antipsychotic dose or replacing orphenadrine with another anticholinergic agent. The corresponding number for biperiden users was 19.3%. Only 11.8% of patients switched to another antipsychotic drug, but they used significantly lower antipsychotic doses than those who stayed on the same drug. The use of anticholinergic antiparkinson agents could be seen as superfluous for at least one-third of patients.

Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents

The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.

Anticholinergic antiparkinson drugs are used to ameliorate extrapyramidal symptoms caused by either Parkinson's disease or antipsychotic drugs, but their use in the treatment of Parkinson's disease is assumed to be in decline. Patients with psychotic conditions have a high prevalence of abuse of drugs, including anticholinergic antiparkinson drugs. Anticholinergic antiparkinson drugs in Norway were primarily prescribed to patients using antipsychotic medication. The risk of abuse of this group of drugs was small, even among patients who probably abused other drugs. The use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinson's disease to the amelioration of extrapyramidal adverse effects induced by antipsychotic drugs. There is a considerable body of data suggesting that anticholinergic antiparkinson drugs have a potential for abuse. The aim was to investigate the use and potential abuse of this class of drugs in Norway. Data were drawn from the Norwegian Prescription Database on sales to a total of 73 964 patients in 2004 of biperiden and orphenadrine, and use in patients with Parkinson's disease or in patients who were also prescribed antipsychotic agents. Possible abuse of these drugs was assessed by the level of use, skewedness of use, indications of drug-seeking behaviour and concomitant use of benzodiazepine tranquillizers, a group of prescription drugs with a recognized potential for abuse. Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's disease by >20 to 1. We found indications of abuse of benzodiazepine tranquillizers among patients using antipsychotics, but there were no clear indications of abuse of anticholinergics, even among patients who were strongly suspected of abuse of benzodiazepines. Anticholinergic antiparkinson drugs were used primarily by patients with psychotic illnesses. These patients have a very high prevalence of legal and illegal drug abuse, but the risk of abuse of anticholinergic antiparkinson drugs seemed small.

Effect of warnings in a medical journal on the use of orphenadrine

This thesis is based on two fundamental questions: Which patients are currently using anticholinergic antiparkinson drugs? Does it matter which anticholinergic antiparkinson drug they are using? These questions were further investigated, using a variety of methods, as follows: Are anticholinergic antiparkinson agents predominantly used to treat Parkinson’s disease or antipsychotic induced extrapyramidal side-effects (EPS)? Is there a high risk of abuse of anticholinergic antiparkinson agents? Can alleged differences in receptor binding profiles of typical first- (FGA) and atypical second (SGA) -generation antipsychotic agents predict concomitant use of anticholinergic agents? Can long-term co-prescription of anticholinergic antiparkinson agents shed some light on the efficacy of antipsychotic agents? Does the literature indicate differences in toxicity and fatality rates of anticholinergic antiparkinson agents? Does an autopsy material indicate differences between anticholinergic agents regarding toxicity and fatality risk? Are warnings in a medical journal against the use of the most toxic anticholinergic agent enough to reduce its use? Can patients stop using anticholinergic agents without further remedies? The thesis has the following conclusions: The overwhelming majority of anticholinergic users were patients concomitantly using antipsychotic agents, presumably for the alleviation of antipsychotic induced EPS. The use of anticholinergics was not particularly skewed and we could not find any other indication of abuse, indicating that concomitant use of anticholinergics can be a proxy for the liability of specific antipsychotic agents to cause EPS. For patients using only one antipsychotic agent, the concurrent use of anticholinergics varied between 0.4% and 26.0%, but largely independently of the distinction between typical and atypical antipsychotics. High D2-receptor antagonism and a high 5-HT2A/D 2- receptor-affinity ratio coincided with the use of anticholinergics. Clozapine and zuclopentixol demonstrated the highest level of prescription persistence in a three-year period. The high prevalence of concomitant use of anticholinergics and zuclopentixol may indicate that the latter was considered efficacious enough to outweigh its probable side-effects. Haloperidol was associated with a mortality three times that of any other antipsychotic agent in the study. Orphenadrine is by far the most toxic anticholinergic antiparkinson agent with a high mortality risk. Warnings in a medical journal against the use of a toxic drug can have an impact on prescription patterns. At least one-third of the patients using anticholinergic antiparkinson agents do not need them.

Enquête de pratiques de prescription des antipsychotiques dans 13 centres hospitaliers du réseau PIC

The commercial introduction of atypical antipsychotics, called second-generation antipsychotics (SGAs), a few years ago, has led to a world-wide reappraisal of the established treatment strategies for people with psychotic or bipolar disorders. They permitted improvements in the pharmacologic management of psychiatric diseases. As compared to conventional neuroleptics or first-generation antipsychotics (FGAs), they promised better efficacy especially on negative symptoms and cognitive impairments of psychiatric diseases and, at the same time, better tolerance on neurological side effects. Now, they have shown other side effects and they have a higher acquisition cost than FGAs. The aim of this paper is to describe and analyse the prescribing practices of antipsychotic drugs in French psychiatric hospitals for adult inpatients and to compare them with other surveys and guidelines. In June 2004, we conducted a one-day, cross-sectional, observational and naturalistic study in 13 hospitals, members of the PIC network. Two thousand one hundred and ninety-two prescriptions with antipsychotic treatment were collected. One thousand one hundred and fifty-four prescriptions (52.6%) included a SGA, but the FGAs were the most prescribed (65.8%; n=2259), principally cyamemazine (24.7%). There was one antipsychotic in 50.7% of prescriptions, two antipsychotics in 42.2%, but the second neuroleptic used was a sedative (82.6%), principally cyamemazine. Multiple antipsychotics were present in 1081 prescriptions (49.3%), with an average number of 1.57 antipsychotics. A mood stabiliser, an antidepressant, an anxiolytic and a hypnotic were coprescribed in respectively 37, 30.5, 65.1 and 41.6%. There were 2.48 psychotropic drugs associated with the principal antipsychotic; in total, with correctors of side-effects of the antipsychotics, there were 3.38 drugs per prescription. The SGAs aimed more often for psychotic (F20-F29) patients (61.9% versus 43.3% with FGAs), who were males (61.4% versus 68%), younger (42.6 years versus 44.1 years; p<0.02), with higher average daily doses, more associated with other neuroleptics (p<0.0004) and less associated with anticholinergic antiparkinsonian agents (p<10(-4)) than FGAs. Compared to other surveys, these results showed that the SGAs have become the first-line treatment for psychiatric disorders. The highest average daily doses corresponded to treatments of psychotic patients and, hence, the values might largely exceed the authorized maximum doses. Furthermore, in more than half of the cases, an FGA, generally a sedative, was associated with an SGA that did not comply with the principle of monotherapy established by the national and international guidelines; that also annulled the expected benefit of the SGAs on the awakening, cognition and the neurological tolerability of the treatment. The coprescriptions of the other psychotropic drugs to neuroleptics also remained the rule in psychiatry, showing all the complexity of pharmacological psychiatric medications. Prescriptions also included treatments for side effects of antipsychotics; even on the prescriptions including the SGAs, there was the coprescription of anticholinergic antiparkinsonian drugs, the deleterious character of which one knows on cognition. This resulted in a difficulty of understanding the prescription for the patient, associated with reduced compliance and increased risks of pharmacological side effects. The heterogeneity of the situations of crisis in psychiatric hospitals could make the strict application of guidelines' recommendations difficult. Nevertheless, the educational interventions in psychopharmacology for patients and the training campaigns for psychiatrists and nurses are necessary to improve the therapeutic management of the patient and ensure him/her optimal quality of life. This kind of survey, far too rare, was very important because it showed the routine clinical settings in which these new drugs were really used. The results showed that SGAs appeared to take the place of the FGAs used in the treatment of psychoses, particularly schizophrenia, but also in the treatment of mood disorders and they reflected actual clinical practices. Other surveys must be conducted to see whether our study confirms the general trend concerning the use of these drugs and, therefore, to reassess these prescribing practices.

Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656

The anticholinergic antiparkinson drug orphenadrine is an antagonist at central and peripheral muscarinic receptors. Orphenadrine intake has recently been linked to QT prolongation and Torsade-de-Pointes tachycardia. So far, inhibitory effects on I (Kr) or cloned HERG channels have not been examined. HERG channels were heterologously expressed in a HEK 293 cell line and in Xenopus oocytes and HERG current was measured using the whole cell patch clamp and the double electrode voltage clamp technique. Orphenadrine inhibits cloned HERG channels in a concentration dependent manner, yielding an IC(50) of 0.85 microM in HEK cells. Onset of block is fast and reversible upon washout. Orphenadrine does not alter the half-maximal activation voltage of HERG channels. There is no shift of the half-maximal steady-state-inactivation voltage. Time constants of direct channel inactivation are not altered significantly and there is no use-dependence of block. HERG blockade is attenuated significantly in mutant channels lacking either of the aromatic pore residues Y652 and F656. In conclusion, we show that the anticholinergic agent orphenadrine is an antagonist at HERG channels. These results provide a novel molecular basis for the reported proarrhythmic side effects of orphenadrine.

Antipsychotic-induced Extrapyramidal Syndromes in Psychiatric Practice: A Case-control Study

While several clinical trials showed that atypical antipsychotics have a low risk of extrapyramidal side effects (EPS), this observation is not undisputed. This study compared the risk of EPS between specific subgroups of antipsychotics. Using the automated dispensing records of a large psychiatric hospital in The Netherlands, we defined cases as first-time users of anticholinergic antiparkinson drugs. Controls were all patients with no recorded use of such medication. Cases and controls were compared with regard to previous use of antipsychotics and relevant co-factors. Out of 1403 patients, we identified 105 cases and 330 controls. Compared to non-users, antipsychotic-users were 10 times more likely to start with anticholinergic antiparkinson medication (adjusted odds ratio: 10.1; 95 CI 4.6-22.3). Depot and non-depot antipsychotics had similar adjusted odds ratios of 10.9 (95 CI 3.7-32.6) and 8.8 (95% CI 3.8-20.4) respectively. Low and high potency antipsychotics gave odds ratios of 3.0 (95% CI 0.9-10.3) versus 10.8 (95% CI 4.7-25.1). Classical and atypical antipsychotics showed comparable odds ratios: 10.0 (95% CI: 4.4-22.5) versus 8.0 (95% CI: 2.6-24.5). Applied doses of classical and atypical antipsychotic drugs were much lower and more equivalent than those used in previous clinical trials. Low potency antipsychotics had a much lower risk of EPS than other antipsychotics. However, we did not corroborate the reduced risk with atypical antipsychotics observed in several clinical trials. This discrepancy may result from the high and non-equivalent doses of classical antipsychotics used in many of these trials.

The striatal muscarinic receptor inhibiting dopamine D1-stimulated adenylyl cyclase activity as a target for anticholinergic antiparkinson drugs

The striatal muscarinic receptor inhibiting dopamine D1-stimulated adenylyl cyclase activity as a target for anticholinergic antiparkinson drugs

Increased Incidence of Levodopa Therapy Following Metoclopramide Use

To determine whether there is an increase in use of antiparkinsonian therapy in older persons taking metoclopramide hydrochloride. Case-control study. New jersey Medicaid program. Medicaid enrollees aged 65 years and older. Cases were patients newly prescribed a levodopa-containing medication (n = 1253); a secondary case group were patients newly prescribed an anticholinergic antiparkinsonian drug (n = 2377). The control group consisted of 16435 Medicaid enrollees older than 65 years who were not users of any antiparkinsonian therapy. We used logistic regression to determine the odds ratio (OR) for the initiation of antiparkinsonian therapy in patients using metoclopramide relative to nonusers, after adjusting for age, sex, race, nursing home residence, exposure to antipsychotic medication, and days hospitalized. Metoclopramide users were three times more likely to begin use of a levodopa-containing medication compared with nonusers (OR = 3.09; 95% confidence interval [Cl], 2.25 to 4.26). Risk increased with increasing daily metoclopramide dose: the OR was 1.19 (95% Cl, 0.50 to 2.81) for more than 0 to 10 mg per day, 3.33 (95% Cl, 1.98 to 5.58) for more than 10 to 20 mg per day, and 5.25 (95% Cl, 1.16 to 8.50) for more than 20mg per day. The effect persisted after adjustment for demographic, health service utilization, and medication use variables. The OR for initiation of anticholinergic antiparkinsonian drugs was also elevated in metoclopramide users. Metoclopramide use confers an increased risk for the initiation of treatment generally reserved for the management of idiopathic Parkinson's disease in patients with drug-induced parkinsonian symptoms, which should be ruled out before starting dopaminergic therapy for this condition.

Anticholinergic antiparkinsonian therapy in outpatients treated with neuroleptic drugs: a prescription survey.

Extrapyramidal adverse effects (EPAs) due to neuroleptic treatment are routinely treated with anti-cholinergic antiparkinsonian drugs (APDs). We studied the use of these drugs in the general population exposed to neuroleptic drugs to improve our knowledge of the epidemiology of EPAs. We selected all the neuroleptic and antiparkinsonian drug prescriptions delivered in the province of Rome (ca. 3,750,000 inhabitants) from 1986 to 1989. During the study period, 10.6% of neuroleptic-treated subjects were concurrently prescribed anticholinergic antiparkinsonian drugs. The influence of different factors on APD prescriptions was evaluated through a logistic regression model. The highest probability of receiving APDs was associated with trifluperidol treatment (odds ratio = 5.0, using chlorpromazine as baseline); among the commonly prescribed neuroleptics, sulpiride, levosulpiride and tiapride chlorydrate had the lowest probability of coprescription with APDs (odds ratios less than 0.1). The probability of being prescribed anticholinergic antiparkinsonian drugs decreased with age and increased with the amount of neuroleptics prescribed. This study surveys a very large sample using a population-based approach, whereas the same topics have previously only been studied in limited inpatient populations.

The dose-response relationship for memory impairment by anticholinergic drugs

Twelve stabilized chronic schizophrenic outpatients receiving maintenance treatment with fluphenazine decanoate plus anticholinergic antiparkinsonian drugs underwent two challenge sessions receiving, in random sequence and double-blind, injections of either benztropine or glycopyrrolate (a peripherally active anticholinergic agent that penetrates the CNS poorly, used as an active placebo). Performance on free recall testing was significantly worse after benztropine than after glycopyrrolate. It has previously been shown that routine clinical doses of anticholinergic antiparkinsonian drugs impair verbal learning relative to a drug-free baseline. Our results suggest that memory impairment continues to further increase as anticholinergic drugs are pushed to the upper limit of the acceptable clinical range.

Effects of Antiparkinsonian Drugs on Muscarinic Receptor Binding in Rat Brain, Heart and Lung

The anticholinergic antiparkinsonian drugs biperiden, benztropine, trihexyphenidyl, methixene, and procyclidine were compared with atropine and pirenzepine, as well as with orphenadrine, amantadine and some standard antidepressives and neuroleptics in their ability to inhibit the binding of tritiated quinuclidinyl benzilate (QNB) to the muscarinic receptors in rat brain cortical tissue. Most of the antiparkinsonian drugs studied were potent inhibitors of (-)3H-QNB binding, when compared to atropine (IC50-value = 0.22 microM), the IC50-values ranging from 0.0084 microM (biperiden) to 0.07 microM (procyclidine). Orphenadrine had a low and amantadine no evident affinity for muscarinic receptors. With the exception of pirenzepine and biperiden the inhibition curves were steep and parallel, giving linear Hill plots with coefficients close to unity. The binding profile of atropine, pirenzepine, and biperiden was further studied in heart and lung tissues, atropine showing only small divergences in its binding to the different tissues, but biperiden and pirenzepine having five to ten times lower affinity in the peripheral tissues than in the brain. The results confirm the high affinity of most of the antiparkinsonian drugs for brain muscarinic receptors. The dissociation constants agree with the average clinical doses of the drugs. It must be remembered, however, that the binding data may represent multiple events at receptor sites because most of the drugs used are mixtures of stereoisomers. Thus further studies using individual enantiomers are needed to compare more directly binding data between the compounds.

Toxic psychosis due to self-administered antiparkinson drug overdosage: A case report

Anticholinergic antiparkinson drugs are psychotoxic and euphorigenic. Abuse of these drugs has been documented. Levodopa, a dopamine precursor used for the symptomatic treatment of idiopathic Parkinson's disease, is potentially psychotoxic too. However, euphorigenic effects of levodopa have not been documented and to the author's knowledge there are no reports of abuse of this drug. The author presents a case of toxic confusional psychosis due to overdosage of two antiparkinson drugs, levodopa and orphenadrine. The motivation for the overdosage was to achieve pleasurable psychic effects. Levodopa should be included among psychotropic drugs with a potential to cause confusional psychotic reactions in non-Parkinsonian patients.

The anticholinergic anti-parkinson drug norakinR selectively inhibits influenza virus replication

The anticholinergic anti-parkinson drug norakinR selectively inhibits influenza virus replication

Drugs for Parkinson's disease reduce tremor induced by physostigmine

The effects of anticholinergic and dopaminergic drugs used for Parkinson's disease were studied on the tremor induced by physostigmine (0.3-3.0 mg/kg) in rats. For the measurement of tremor a new electronic device was employed. Atropine (0.3-1.2 mg/kg) and biperiden (0.01-1.0 mg/kg) reduced the physostigmine-induced tremor in a dose-related manner and could abolish it. Biperiden was less potent than atropine. Methylatropine in a dose of 1.2 mg/kg slightly inhibited the tremor. Amantadine (0.3-3.0 mg/kg) reduced the tremor but only to a certain degree. Bromocriptine (0.1-10.0 mg/kg) reduced it in a manner that was not dose-related. Pimozide potentiated the tremor in the dose of 0.2 mg/kg but not in larger doses. At the onset of the tremor, a small decrease in rectal temperature occurred. The hypothermia lasted significantly longer than the tremor. Neither the anticholinergic nor the dopaminergic anti-Parkinson drugs altered the hypothermic effect of physostigmine. The results show that those anti-Parkinson drugs, which act by increasing the dopaminergic activity can counteract the tremor induced by physostigmine. However, these drugs are clearly less active than th anticholinergic anti-Parkinson drugs.

Case report of propranolol (inderal) pharmacotherapy for neuroleptic-induced akathisia and tremor

1. 1. This case report describes a schizophrenic patient who developed akathisia and tremor following neuroleptic pharmacotherapy with fluphenazine decanoate. The patient also suffered from familial (benign essential) tremor. 2. 2. The patient's neuroleptic-induced extrapyramidal side effects were not relieved by anti-cholinergic antiparkinson drugs or by phenobarbital. The patient was started on propranolol 10 mg b.i.d. She was also started on diazepam 5 mg t.i.d. for anxiety. The diazepam dose was held constant and propranolol was gradually increased to 40 mg q.i.d. 3. 3. The patient's extrapyramidal symptomatology gradually resolved over the course of one month, during which time the propranolol dose was being steadily increased. Propranolol also effectively controlled her familial tremor. 4. 4. After nine months as an outpatient, during which time the patient was neuroleptic-free, she developed psychotic decompensation for which she was treated with thiothixene. Akathisia or tremor did not develop, possibly because the patient was taking propranolol simultaneously. 5. 5. Propranolol may be useful for treating neuroleptic-induced akathisia. This requires systematic investigation with open and controlled trials.