piperidines and Dystonia

We herein report an 81-year-old woman with Alzheimer's disease (AD) in who donepezil, a cholinesterase inhibitor (ChEI), caused cervical dystonia. The patient had a two-year history of progressive memory disturbance fulfilling the NINCDS-ADRDA criteria for probable AD. Mini-Mental State Examination score was 19/30. The remaining examination was normal. After a single administration of donepezil (5 mg/day) for 10 months, she complained of dropped head. Neurological examination and electrophysiological studies supported a diagnosis of cervical dystonia. Antecollis disappeared completely at 6 weeks after cessation of donepezil. Dystonic posture can occur at various timings of ChEI use. Physicians should pay more attention to rapidly progressive cervical dystonia in ChEI-treated AD patients.

Topics: Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Dystonia; Female; Humans; Indans; Piperidines; Postural Balance

Topics: Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cohort Studies; Donepezil; Dystonia; Galantamine; Humans; Indans; Male; Piperidines; Syndrome

The effectiveness of conventional neuroleptics in schizophrenia is often limited by extrapyramidal side effects (EPS), which are known to contribute to poor compliance and relapse. However, there is now evidence that drugs that block 5-HT2 receptors as well as D2 receptors have better EPS profiles. Risperidone has these pharmacologic properties. In two large clinical trials, risperidone (2, 6, 10, 16 mg/day or 4, 8, 12, 16 mg/day) was compared with either placebo and haloperidol (20 mg/day) or risperidone (1 mg/day) and haloperidol (10 mg/day). Extrapyramidal side effects were assessed using the Extrapyramidal Symptom Rating Scale and by recording the use of anticholinergic medication. Other adverse effects were assessed using the UKU Side Effects Scale. In both studies, the severity of EPS in the risperidone groups was significantly less than in the haloperidol group. In the placebo-controlled study, doses of 2 and 6 mg/day of risperidone produced no worse EPS than placebo. Other side effects were minor, and included brief hypotension (mediated via alpha-blockade) and weight gain. Overall, risperidone at antipsychotic doses was better tolerated than haloperidol.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Clinical Trials as Topic; Dyskinesia, Drug-Induced; Dystonia; Haloperidol; Humans; Isoxazoles; Piperidines; Risperidone; Schizophrenia

Topics: Adolescent; Adult; Aged; Basal Ganglia Diseases; Benzamides; Butyrophenones; Child; Drug-Related Side Effects and Adverse Reactions; Dystonia; Extrapyramidal Tracts; Female; Humans; Male; Middle Aged; Muscle Hypertonia; Muscle Rigidity; Parkinson Disease, Secondary; Phenothiazines; Piperazines; Piperidines; Reserpine; Thioxanthenes

To assess the efficacy and safety of high-dose (up to 20 mg/day) cabergoline in Parkinson's disease (PD) patients with motor fluctuations and/or dyskinesias.. Thirty-four PD patients had cabergoline up-titrated and their levodopa (L-dopa) reduced over a maximum of 20 weeks, followed by at least 6 weeks steady cabergoline dosing. Primary endpoint was change in mean hyperkinesia intensity at the final visit (week 26).. Mean (+/- SD) cabergoline was increased from 6.43 +/- 2.66 to 12.78 +/- 5.67 mg/day and mean L-dopa reduced from 606.6 +/- 263.9 to 370.6 +/- 192.5 mg/day. A significant reduction (P < 0.001) in mean hyperkinesia intensity occurred from baseline (day 0) to week 26. Improvements in 'on with dyskinesias', mean dystonia intensity (P < 0.05), time spent in 'severe off' condition, severity of 'off' periods as well as clinical/patient global impression, and health-related quality of life were observed. Twenty-four drug-related adverse events were recorded of which four were regarded as serious.. High-dose cabergoline was well tolerated and provided significant improvements in the Parkinson symptomatology and a reduced requirement for L-dopa.

Topics: Adolescent; Adult; Aged; Amantadine; Antiparkinson Agents; Cabergoline; Catechols; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Humans; Levodopa; Middle Aged; Nitriles; Parkinson Disease; Piperidines; Prospective Studies; Quality of Life; Selegiline; Severity of Illness Index; Treatment Outcome

1. This open clinical trial (N = 7) measured the course of severe tardive dystonia in chronic psychiatric patients after discontinuation of neuroleptics and subsequent use of clozapine. 2. The dystonia was regularly assessed using the Fahn-Marsden Rating Scale. The eventual concomitant tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale. The mean follow up was 103 weeks. 3. The results for the tardive dystonia: four patients recovered totally, two improved considerably and one did not recover. 4. The results for the concomitant tardive dyskinesia: five of the seven patients had also dyskinesia, one patient had a total, two a partly remission, one had a very fluctuating course, and one patient worsened. Another patient developed dyskinesia. 5. It is suggested to consider clozapine for patients with tardive dystonia who have to continue antipsychotic treatment.

Topics: Adult; Clozapine; Dystonia; Female; Humans; Male; Middle Aged; Piperidines; Triazoles

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dystonia; Female; Humans; Olanzapine; Piperazines; Piperidines; Risperidone; Schizophrenia; Young Adult

Deep brain stimulation (DBS) has become accepted therapy for intractable dystonia and other movement disorders. The accurate placement of DBS electrodes into the globus pallidus internus is assisted by unimpaired microelectrode recordings (MERs). Many anesthetic and sedative drugs interfere with MERs, requiring the patient to be awake for target localization and neurological testing during the procedure. In this study, a novel anesthetic technique was investigated in pediatric DBS to preserve MERs.. In this paper, the authors describe a sedative/anesthetic technique using ketamine, remifentanil, dexmedetomidine, and nicardipine in 6 pediatric patients, in whom the avoidance of GABAergic stimulating drugs permitted excellent surgical conditions with no detrimental effects on intraoperative MERs. The quality of the MERs, and the frequency of its use in making electrode placement decisions, was reviewed.. All 6 patients had good-quality MERs. The data were of sufficient quality to make a total of 9 trajectory adjustments.. Microelectrode recordings in pediatric DBS can be preserved with a combination of dexmedetomidine and ketamine, remifentanil, and nicardipine. This preservation of MERs is particularly crucial in electrode placement in children.

Topics: Adolescent; Anesthesia; Anesthetics, Combined; Anesthetics, Dissociative; Antihypertensive Agents; Child; Deep Brain Stimulation; Dexmedetomidine; Dystonia; Dystonic Disorders; Female; Humans; Hypnotics and Sedatives; Ketamine; Male; Microelectrodes; Neurophysiological Monitoring; Nicardipine; Piperidines; Remifentanil; Sleep; Wakefulness

Topics: Antitussive Agents; Child; Cough; Dystonia; Female; Humans; Piperidines

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Dystonia; Female; Humans; Indans; Memory Disorders; Piperidines; Postural Balance; Sensation Disorders

(1) Three cholinesterase inhibitors are marketed in France for the treatment of Alzheimer's disease: donepezil, galantamine and rivastigmine. Tremor and dystonia are known adverse effects of cholinesterase inhibitors. (2) In patients with Parkinson's disease who have cognitive disorders, or in patients with Lewy body dementia, exacerbations of parkinsonism and tremor have been observed during treatment with cholinesterase inhibitors at normal doses. The disorders were reversible on withdrawal of the cholinesterase inhibitor. (3) Withdrawal of cholinesterase inhibitors should be considered if gait disorders, falls or parkinsonism occur or worsen during treatment.

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Dystonia; France; Galantamine; Humans; Indans; Lewy Body Disease; Parkinson Disease; Phenylcarbamates; Piperidines; Tremor

Success in treating patients with progressive supranuclear palsy and corticobasal degeneration remains exceedingly low. This finding probably relates to the widespread distribution of the pathological changes that account for the varied and complex spectrum of clinical manifestations. Dopaminergic drugs are regularly used for the parkinsonian features; however, these rarely result in more than modest benefit, and when better or sustained responses are obtained, as sometimes occurs in progressive supranuclear palsy, the clinical features are atypical and diagnosis is often delayed or not made in life. A variety of other treatments have been used in both disorders, sometimes directed at other specific features such as dystonia or myoclonus, and these treatments will be reviewed. Greater success in treating these disorders will require advances in our understanding of their cause(s) or the pathogenetic mechanisms underlying the neurodegenerative processes. The similarities in the molecular pathology of these four-repeat tauopathies suggests that important advances in the management of one will have a definite impact on the treatment of the other.

Topics: Amantadine; Cerebral Cortex; Cholinesterase Inhibitors; Corpus Striatum; Donepezil; Dopamine Agents; Dopamine Agonists; Dystonia; Globus Pallidus; Humans; Indans; Levodopa; Nerve Degeneration; Piperidines; Substantia Nigra; Supranuclear Palsy, Progressive

Previous studies suggested that glutamatergic overactivity contributes to the manifestation of dystonia in the dt(sz) mutant hamster, a model of idiopathic paroxysmal dyskinesia in which dystonic episodes occur in response to mild stress. Therefore, the role of polyamines, known as positive modulators of NMDA receptors, was examined in the present study. The levels of polyamines (putrescine, spermidine, spermine) were determined in forebrain, cerebellum and brainstem in dt(sz) hamsters at an age of most marked expression of dystonia (32 days) and in age-matched non-dystonic control hamsters. Spermine was found to be significantly increased in the forebrain (35%) of dystonic animals, while spermidine was unaltered in dystonic brains and only a moderate increase in putrescine (12%) was detected in the cerebellum of dt(sz) mutants. In view of enhanced spermine levels, the effect of the putative polyamine receptor antagonist ifenprodil on the severity of dystonia was examined in dystonic hamsters. Ifenprodil (5-40 mg/kg i.p.) failed to exert a beneficial effect, but even aggravated dystonia in the dt(sz) mutant at higher doses. These data together with previous pharmacological findings in mutant hamsters do not completely exclude a pathophysiological role of enhanced polyamine levels but suggest that overstimulation of NMDA receptors which contain NR2B subunits by enhanced spermine levels is not involved in the dystonic syndrome.

Topics: Aging; Animals; Brain; Case-Control Studies; Chorea; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Dystonia; Excitatory Amino Acid Agents; Mutation; Piperidines; Polyamines; Receptors, N-Methyl-D-Aspartate; Severity of Illness Index

Previous studies have shown beneficial effects of the cannabinoid CB(1)/CB(2) receptor agonist (R)-4,5-dihydro-2-methyl-4-(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo [3,2,1-ij]quinolin-6-one mesylate (WIN 55,212-2) in dt(sz) mutant hamsters, a model of idiopathic paroxysmal dystonia (dyskinesia). To examine the pathophysiological significance of the cannabinergic system in the dystonic syndrome, the effect of the cannabinoid CB(1) receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR 141716A) on severity of dystonia was investigated in dt(sz) mutants which exhibit episodes of dystonic and choreoathetotic disturbances in response to mild stress. SR 141716A (5 and 10 mg/kg i.p.) failed to exert any effects on the severity of dystonia. While the antidystonic efficacy of WIN 55,212-2 (5 mg/kg i.p.) was confirmed, cannabidiol (which has low affinity to cannabinoid receptors) tended to delay the progression of dystonia only at a high dose (150 mg/kg i.p.). The antidystonic and cataleptic effects of WIN 55,212-2 (5 mg/kg i.p.) were completely antagonized by pretreatment with SR 141716A at doses of 2.5 mg/kg (catalepsy) and 10 mg/kg (antidystonic efficacy). These data indicate that the antidystonic efficacy of WIN 55,212-2 is selectively mediated via CB(1) receptors. The lack of prodystonic effects of SR 141716A together with only moderate antidystonic effects of WIN 55,212-2 suggests that reduced activation of cannabinoid CB(1) receptors by endocannabinoids is not critically involved in the dystonic syndrome. In view of previous pathophysiological findings in mutant hamsters, the antidystonic efficacy of WIN 55,212-2 can be explained by modulation of different neurotransmitter systems within the basal ganglia.

Topics: Animals; Benzoxazines; Cannabidiol; Cannabinoid Receptor Modulators; Cannabinoids; Chorea; Cricetinae; Disease Models, Animal; Dystonia; Female; Male; Mesocricetus; Morpholines; Naphthalenes; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Dystonia; Humans; Indans; Male; Middle Aged; Piperidines; Psychomotor Disorders

We report two patients who developed Pisa syndrome after treatment with cholinesterase inhibitors--cognition-enhancing novel agents for patients with Alzheimer's disease. Cholinergic excess could be another factor in Pisa syndrome, especially in cholinergically-imbalanced Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Carbamates; Cholinesterase Inhibitors; Donepezil; Dopamine Antagonists; Dystonia; Female; Humans; Indans; Memory Disorders; Middle Aged; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Piperidines; Posture; Psychomotor Agitation; Risperidone; Rivastigmine; Syndrome

The case is reported of an infant presenting paroxysmal dystonia during cisapride theraphy. We suggest that this drug, a substituted benzamide, probably interfered with the age-related modification of striatal neurotransmitters, provoking extrapyramidal symptoms. Considering the widespread use of cisapride in early infancy for the treatment of gastrointestinal disorders, attention must be drawn to this possible side effect.

Topics: Cisapride; Dystonia; Female; Humans; Infant; Piperidines; Prognosis

To clarify clinical roles of sigma receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of sigma receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative sigma receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as sigma receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of potency in induction of dystonia and sigma receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for sigma receptors, it never produced dystonia by itself. On the other hand, combined injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is suggested that typical neuroleptics such as haloperidol act agonistic and atypical neuroleptics such as BMY-14802 act antagonistic at rubral sigma receptors in the induction of neck dystonia.

Topics: Animals; Antipsychotic Agents; Dibenzothiepins; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dystonia; Guanidines; Haloperidol; Male; Microinjections; Nerve Tissue Proteins; Perphenazine; Piperidines; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Receptors, sigma; Red Nucleus; Sulpiride; Torticollis

Topics: Alzheimer Disease; Botulinum Toxins; Chlorpromazine; Dystonia; Female; Humans; Isoxazoles; Middle Aged; Neck Muscles; Phenytoin; Piperidines; Risperidone; Valproic Acid

Topics: Adult; Antipsychotic Agents; Clozapine; Dystonia; Humans; Isoxazoles; Male; Piperidines; Risperidone; Schizophrenia

A 43-year-old woman with gastroesophageal reflux disease developed a dystonic-like reaction approximately 3 days after starting oral cisapride therapy. Office evaluation revealed a patient who moved her head rhythmically from side to side as she stared into space, generally unresponsive to external stimuli. She had increased tone of the sternocleidomastoid muscles bilaterally, with occasional tongue protrusion, and a slow shuffling gait. Following discontinuation of cisapride, the patient recovered completely.

Topics: Adult; Cisapride; Diphenhydramine; Dystonia; Female; Gastroesophageal Reflux; Humans; Parasympathomimetics; Piperidines

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Dystonia; Humans; Isoxazoles; Male; Neurologic Examination; Piperidines; Risperidone; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.

Topics: Administration, Oral; Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Benzothiazoles; Cebus; Disease Models, Animal; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dyskinesia, Drug-Induced; Dystonia; Ergolines; Female; Haloperidol; Lisuride; Male; Piperidines; Pramipexole; Quinpirole; Raclopride; Salicylamides; Thiazoles

Three (+)-benzomorphans that bind to sigma receptors produced dystonia in a dose-related manner when microinjected into the red nucleus of rats. Two lines of evidence suggest that these effects were related to the sigma-binding properties of the compounds. First, the behavioral potency of the (+)-benzomorphans and other active sigma compounds correlated highly with their affinities for [3H]1,3-di-o-tolylguanidine-labelled sigma receptors in the rat brain (r = .94). Second, similar intrarubral injections of non-sigma ligands were without effect: various vehicles, a structurally related (+)-opiate with no affinity for sigma receptors, and selective dopaminergic and serotonergic compounds failed to significantly alter the normal posture of rats. The only ligand in this study that binds with high affinity to sigma receptors, but failed to elicit torsional head movements was (+)-[3-(3-hydroxyphenyl)-N-(1-propyl)piperidine] [(+)-3PPP], a ligand with mixed activity at sigma and dopamine receptors. Since (+)-3PPP failed to produce an effect on its own and also failed to attenuate the dystonia produced by another sigma ligand (DTG), it may interact with a non-sigma mechanism or with a different sigma receptor type from the other compounds.

Topics: Animals; Benzomorphans; Drug Interactions; Dystonia; Male; Microinjections; Morphinans; Piperidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, sigma; Red Nucleus

The acute effect of intravenous injections of biperiden and clonazepam was investigated in 14 patients with various forms of dystonia (segmental dystonia, 2; generalized dystonia, 6; and Meige's syndrome, 6). Eleven patients had primary dystonia, and 3 patients had a secondary form of dystonia. Doses of 5 mg of biperiden reduced dystonia when evaluated by total scores, global scores, and subjective scores. Two patients had marked side effects in the form of dizziness. Doses of 1 mg of clonazepam significantly reduced total scores and subjective scores, but the reduction in global score was insignificant. No patient had marked side effects following injection with clonazepam. These results correspond with earlier investigations of the long-term effects of anticholinergics and benzodiazepines. It is concluded that in some cases, intravenous injections can be used as a test for evaluating both effects and side effects of antidystonic medication prior to the institution of oral treatment. Long-term intravenous treatment might be considered in individual cases.

Topics: Adult; Biperiden; Clonazepam; Dystonia; Female; Humans; Injections, Intravenous; Male; Middle Aged; Piperidines

Topics: Adult; Benzimidazoles; Domperidone; Dystonia; Female; Humans; Infusions, Parenteral; Piperidines