Journal ArticleDOI
Behavioral effects of clozapine, pimavanserin, and quetiapine in rodent models of Parkinson's disease and Parkinson's disease psychosis: evaluation of therapeutic ratios.
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TLDR
It is suggested that a selective 5-HT2A inverse agonist/antagonist, such as pimavanserin, may provide distinct advantages compared with clozapine or quetiapine as a therapy for PDP.Abstract:
No safe, tolerated, and effective treatment for Parkinson's disease psychosis (PDP) is available; however, clozapine and quetiapine are often used off-label. An ideal PDP drug should have a therapeutic window that alleviates psychotic symptoms at doses that allow for maintained motor control and do not cause sedation. The present study determined the effective doses of quetiapine, clozapine, and the nondopaminergic, selective 5-HT2A inverse agonist/antagonist, pimavanserin, in an animal model of PDP and compared them with the doses that caused dopamine blockade and sedation. Augmented amphetamine-induced locomotion in rats with bilateral substantia nigra lesions was used to assess antipsychotic efficacy, whereas blockade of apomorphine-induced rotations in rats with unilateral 6-hydroxydopamine lesions was used to assess antidopaminergic action and reduction in spontaneous locomotion was used to assess sedation. The estimated therapeutic ratios for clozapine and quetiapine varied between 0.81 and 3.3. In contrast, the estimated therapeutic ratios for pimavanserin were at or above 170. These results suggest that a selective 5-HT2A inverse agonist/antagonist, such as pimavanserin, may provide distinct advantages compared with clozapine or quetiapine as a therapy for PDP.read more
Citations
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Journal ArticleDOI
Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs.
TL;DR: The challenges associated with the development of novel therapies for Parkinson disease are discussed, highlighting emerging agents that aim to target cell death, as well as new targets offering a symptomatic approach to managing features and progression of the disease.
Journal ArticleDOI
On the discovery and development of pimavanserin: a novel drug candidate for Parkinson's psychosis
TL;DR: Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III, and may offer a viable treatment option for patients suffering from PDP.
Journal ArticleDOI
Treatment of Psychosis and Dementia in Parkinson’s Disease
TL;DR: For treating PD psychosis, a first step would be eliminating confounding variables, such as delirium, infections, or toxic-metabolic imbalances, followed by simplifying parkinsonian medications as tolerated, if additional treatment is warranted after such interventions.
Journal ArticleDOI
Mechanism of action of pimavanserin in Parkinson’s disease psychosis: targeting serotonin 5HT2A and 5HT2C receptors
TL;DR: Pimavanserin, a novel agent approved for the treatment of Parkinson’s disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/ inverse agonists actions at5HT2C receptors.
Journal ArticleDOI
CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism?
TL;DR: Previous methods for identifying and validating novel targets for CNS drug discovery are outlined, and potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders are discussed.
References
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Journal ArticleDOI
Risk factors for nursing home placement in advanced Parkinson's disease.
TL;DR: Data suggest that vigorous efforts to control hallucinations may be warranted to prevent nursing home placement, and there was no risk factor synergy for hallucinations, motor disability, and mental impairment.
Journal ArticleDOI
A 12-year population-based study of psychosis in Parkinson disease
Elin Bjelland Forsaa,Jan Petter Larsen,Tore Wentzel-Larsen,Christopher G. Goetz,Glenn T. Stebbins,Dag Aarsland,Guido Alves +6 more
TL;DR: Psychotic symptoms affect most patients with PD, with increased risk in those with higher age at onset, need for high doses of dopaminergic drugs, and probable REM sleep behavior disorder, place PDP within a symptom complex signaling a malignant disease course.
Journal ArticleDOI
Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease
TL;DR: Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo.
Journal ArticleDOI
Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind labeled study of 3 months' duration.
TL;DR: This double‐blind study did not show a beneficial effect of QTP for the treatment of DIP in Parkinson's disease, and the high rate of withdrawal probably influenced the results.
Journal ArticleDOI
Serotonin 2A Receptors and Visual Hallucinations in Parkinson Disease
Bénédicte Ballanger,Antonio P. Strafella,Thilo van Eimeren,Mateusz Zurowski,Pablo Rusjan,Sylvain Houle,Susan H. Fox +6 more
TL;DR: This pilot study provides the first in vivo evidence suggesting a role for serotonin 2A receptors in mediating VHs via the ventral visual pathway in PD, and treatment studies should be performed using selective serotonin2A receptor antagonists.
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