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Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease. (PIMPARK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03947216
Recruitment Status : Recruiting
First Posted : May 13, 2019
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
NS-PARK
EUCLID
F-CRIN
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

Brief Summary:

There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA).

Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS).

Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD.

Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice.

Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD.

Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD.

This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.


Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Active drug: pimavanserin 17mg (2 strength tablets) Drug: Placebo: 2 tablets containing same excipients except active compound Behavioral: Assessment of severity of ICD (impulse control disorders) Behavioral: Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors Behavioral: Assessment of quality of life Behavioral: Assessment of depression Behavioral: Assessment of cognition Behavioral: Assessment of severity of Parkinson Disease Procedure: Blood analysis Procedure: Cardiac monitoring Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of Pimavanserin Efficacy for the Treatment of Impulse Control Disorders in Parkinson's Disease
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PIMAVANSERIN
In this arm, each patient will take orally, once daily 2 tablets of active drug pimavanserin of 17mg each and this during the 8-weeks treatment period.
Drug: Active drug: pimavanserin 17mg (2 strength tablets)
Pimavanserin 17mg (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)

Behavioral: Assessment of severity of ICD (impulse control disorders)
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors
Hyper- and hypodopaminergic behaviors (Ardouin's scale); Movement disorders society sponsored unified Parkinson's disease rating scale (MDS-UPDR), and daytime and night time sleep by scale for outcomes in Parkinson's disease SLEEP (SCOPA-SLEEP) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of quality of life
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of depression
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)

Behavioral: Assessment of cognition
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.

Behavioral: Assessment of severity of Parkinson Disease
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)

Procedure: Blood analysis
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56

Procedure: Cardiac monitoring
Electrocardiogram will be realized at day 0, 28 and 56.

Placebo Comparator: PLACEBO
In this arm, each patient will take orally, once daily, 2 tablets of matching placebo (containing all of the same excipients except for the active compound) and this during the 8-weeks treatment period.
Drug: Placebo: 2 tablets containing same excipients except active compound
Placebo (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)

Behavioral: Assessment of severity of ICD (impulse control disorders)
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors
Hyper- and hypodopaminergic behaviors (Ardouin's scale); Movement disorders society sponsored unified Parkinson's disease rating scale (MDS-UPDR), and daytime and night time sleep by scale for outcomes in Parkinson's disease SLEEP (SCOPA-SLEEP) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of quality of life
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)

Behavioral: Assessment of depression
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)

Behavioral: Assessment of cognition
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.

Behavioral: Assessment of severity of Parkinson Disease
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)

Procedure: Blood analysis
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56

Procedure: Cardiac monitoring
Electrocardiogram will be realized at day 0, 28 and 56.




Primary Outcome Measures :
  1. Change in ICD (Impulsive Control Disorders) severity after 8 weeks of treatment evaluated by QUestionnaire for Impulse-compulsive disorder in Parkinson's disease Rating Scale (QUIP-RS). [ Time Frame: at day 0 and week 8 ]

    The primary endpoint of this study will be assessed in both arms using the total form of QUIP-RS.

    QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with ICDs), each applied to the 4 ICDs (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point Likert scale (score 0-4 for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16 and the total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112, with a higher score indicating greater severity (ie, frequency) of symptoms.



Secondary Outcome Measures :
  1. Change SCale for Outcomes in Parkinson's disease - Sleep (SCOPA-SLEEP) score after 4 and 8 weeks of treatment [ Time Frame: At day 0, week 4 and week 8 ]
    The SCOPA-SLEEP is a specific Parkinson's disease rating scale for assessing nighttime sleep (NS) problems and daytime sleepiness (DS) in the past month. The NS subscale has 5 items, scored from 0 (not at all) to 3 (a lot). The DS subscale is composed of 6 items with response options ranging from 0 (never) to 3 (often) with a higher total score indicating greater severity of sleep problems.

  2. Change in Movement Disorders Society-sponsored Unified Parkinson's Disease Rating scale (MDS-UPDRS) scores after 4 and 8 weeks of treatment [ Time Frame: At day 0, week 4 and week 8 ]
    MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. The four parts contains 64 items which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Negative changes from baseline values indicate improvement.

  3. Change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores after 4 and 8 weeks of treatment [ Time Frame: At day 0, week 4 and week 8 ]
    MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6 and the overall score ranges from 0 to 60 with higher MADRS score indicating more severe depression.

  4. Change in Ardouin's scale scores after 4 and 8 weeks of treatment [ Time Frame: At day 0, week 4 and week 8 ]
    The Ardouin's scale is a validated instrument using a structured and standardised interview composed of 21 items specifically designed to assess mood and behaviour with a view to quantifying changes related to Parkinson's Disease, to dopaminergic medication, and to non-motor fluctuations. Each item is scored from 0 (absent) to 4 (severe).

  5. Change in the rate of Clinical Global Impression Severity (CGIS) scale after 4, 8 and 16 weeks of treatment [ Time Frame: At day 0, week 4, week 8 and week 16 ]
    Severity of PD will be assessed in both arms using CGIS scale: the CGI-S is a 7-point scale that requires the rating of the severity of the patient's illness at the time of assessment. Possible ratings are: 1: Normal, not at all ill; 2: Borderline mentally ill; 3: Mildly ill; 4: Moderately ill ; 5: Markedly ill; 6: Severely ill; 7: Among the most extremely ill patients

  6. Change in ICD (Impulsive Control Disorders) severity after 4 weeks of treatment evaluated by QUIP-RS. [ Time Frame: At day 0 and week 4 ]
    Global functioning and severity of the disease will be assessed in both arms by QUIP-RS has 4 primary questions each applied to the 4 ICDs and 3 related disorders It uses a 5-point Likert scale and a higher score indicating greater severity (ie, frequency) of symptoms.

  7. Changes in quality of life measured by Parkinson's Disease Questionnaire (PDQ-39) scores after 4 and 8 weeks of treatment [ Time Frame: At day 0, week 4 and week 8 ]
    Functioning and well-being of patients during the preceding month will be assessed in both arms by 39 questions of the self-administered Parkinson's Disease Questionnaire (PQD-39). Each question is scored from 0 (never) to 4 (always), the higher score indicating higher impact of illness in quality of life.

  8. Change in Zarit scale scores after 4 and 8 weeks of treatment for caregivers [ Time Frame: At day 0, week 4 and week 8 ]
    The burden of the patient's functional and behavioural worsening and to home care will be assessed to the caregiver in both arms by the Zarit Burden scale. It is composed of 22 items to measure the magnitude of the burden experienced by the caregiver. Each item is scored from 0 (never) to 4 (almost always). With a higher score indicating a greater load suffered by the caregiver.


Other Outcome Measures:
  1. Total number of adverse events and serious adverse events [ Time Frame: At week 16 ]
    Open-ended questionnaire will be used in both arms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient with PD according to the UKPDSBB (UK Parkinson's Disease Society Brain Bank) criteria for at least 1 year before randomization
  2. Patient, man or woman, aged from 35 to 75 years old
  3. Patient with moderately severe ICD defined as: a combined ICD total score (defined as the sum of the 4 ICD sub-scores (pathological gambling + buying + hypersexuality + eating)) 10 or, at least one of the 4 ICD sub-scores in the following range:

    1. "pathological gambling" sub-score from 6 to 12 (included),
    2. "buying" sub-score from 8 to 12 (included),
    3. "hypersexuality" sub-score from 8 to 12,
    4. "eating" sub-score from 7 to 12 (included) The use of "lower" margins will guarantee that the patients will present with behavioral disturbances severe enough to justify pimavanserin treatment. On the other hand, the use of "upper" margins will guarantee that the patients included in the trial will not suffer from ICD severe enough to question ethically the use of placebo during the 8 weeks of the treatment
  4. ICD onset after PD onset and after initiation of dopaminergic drugs
  5. Patient treated by dopaminergic drugs for at least 3 months before randomization
  6. Patient treated by a stable regimen of levodopa, dopamine agonists, COMT (Catechol-O-MethylTransferase) and MAOB (Monoamine oxidase B) inhibitors, amantadine, anticholinergic, antidepressant and benzodiazepine for at least 1 month before the randomization and be willing to remain on the same doses throughout the course of their participation in the trial
  7. Patient with health insurance
  8. Patient/ guardian / curator who sign the written informed consent
  9. For women of childbearing potential, use of an effective contraception method* for at least 1 month prior to randomization until 8 weeks after the last dose of study drug administration. Women who do not have an effective contraception* must : have had her last natural menstruation ≥24 months prior to the selection visit, or have been surgically sterilized prior to the selection visit, or have had a hysterectomy prior to the selection visit.

Exclusion Criteria:

  1. Patient suffering from another parkinsonian syndrome (multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, corticobasal degeneration)
  2. Patient who have a known hypersensitivity to the study treatment, based on known allergies to drugs of the same class
  3. Stroke, uncontrolled serious medical illness, myocardial infarction, congestive heart failure, cardiac function disorders, within 6 months before randomization
  4. Patient with history of long QT syndrome
  5. Patient with long QT interval detected with ECG at inclusion visit (> 450 ms)
  6. Patient treated with antipsychotic drugs during the last three months before randomization.
  7. Patient treated with concomitant medications leading to torsade de pointes (TdP) (please refer to medications list with known risks of TdP on appendix XVII.5.10 and check website https://crediblemeds.org/index.php/tools/ for the most up-to-date information
  8. Patient with hydro-electrolytic troubles, particularly hypokaliemia or hypocalcemia not corrected, at inclusion visit
  9. Patient treated with a strong inhibitor of CYP3A4: azole antifungals, rotease inhibitors, macrolides, without discontinuation ≥ 5 half-lives before randomization
  10. Patient treated with medicinal plants interacting with CYP3A4 (Echinacea (E.purpurea, E.angustifolia and E.pallida), Piperina, Artemisia, St. John's Wort et Ginkgo
  11. Patient with Montreal Cognitive Assessment (MoCA) score < 20 (to exclude patients likely with dementia) at inclusion visit
  12. Patient suffering from severe depression or marked suicidal thoughts (score > 3 on the suicidal thoughts item of the MADRS) at inclusion visit
  13. History of Deep Brain Stimulation (DBS) within the past year before randomization
  14. Patient suffering from a cancer
  15. Patient suffering from severe renal impairment define as Creatinie clairance CrCL<30 mL/min, Cockcroft-Gault at inclusion visit
  16. Clinically significant hepatic impairment
  17. Current participation in another research involving human beings of category 1 or 2
  18. Patient with language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator, should not participate in the trial
  19. Treatment with an investigational treatment within 30 days prior to randomization
  20. Woman pregnant, nursing or of childbearing potential age without effective contraception methods or intends to become pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03947216


Contacts
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Contact: Mathieu ANHEIM, MD +33 3 88 12 85 35 mathieu.anheim@chru-strasbourg.fr
Contact: Olivier RASCOL, MD +33 5 61 14 59 62 olivier.rascol@univ-tlse3.fr

Locations
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France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU d'Amien, Hopital Sud Not yet recruiting
Amiens, France, 80054
Contact: Pierre KRYSTKOWIAK, MD    3 3 22 66 82 40    krystkowiak.pierre@chu-amiens.fr   
Principal Investigator: Pierre KRYSTKOWIAK, MD         
SERVICE DE NEUROLOGIE C, Unité mouvement anormaux/Centre expert Parkinson, CHU de Lyon, Hopital neurologique Pierre Wertheimer Not yet recruiting
Bron, France, 69677
Contact: Stephane THOBOIS, MD    +33 4 72 35 72 1    stephane.thobois@chu-lyon.fr   
Principal Investigator: Stephane THOBOIS, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU Clermont-Ferrand, Hopital Gabriel Montpied Not yet recruiting
Clermont-Ferrand, France, 63003
Contact: Franck DURIF, MD    33 4 73 75 22 00    fdurif@chu-clermontferrand.fr   
Principal Investigator: Franck DURIF, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, Hopital Henri Montdor Not yet recruiting
Créteil, France, 94010
Contact: Philippe REMY, MD    +33 1 49 81 43 53    neuro-philippe.remy@hmn.aphp.fr   
Principal Investigator: Philippe REMY, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Grenoble Alpes Not yet recruiting
Grenoble, France, 38043
Contact: Valérie FRAIX, MD    +33 4 76 76 94 52    vfraix@chu-grenoble.fr   
Principal Investigator: Valérie FRAIX, MD         
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, CHU de Lille, Hopital Roger Salengro Not yet recruiting
Lille, France, 59037
Contact: Luc DEFEBVRE, MD    +33 3 20 44 67 30    Luc.DEFEBVRE@CHRU-LILLE.FR   
Principal Investigator: Luc DEFEBVRE, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Limoges Not yet recruiting
Limoges, France, 87042
Contact: Frederic TORNY, MD    +33 5 55 05 65 60    frederic.torny@chu-limoges.fr   
Principal Investigator: Frederic Torny, MD         
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, Hopital de la Timone Not yet recruiting
Marseille, France, 13385
Contact: Jean-Philippe AZULAY, MD    +33 4 91 38 43 33    Jean-philippe.AZULAY@ap-hm.fr   
Principal Investigator: Jean-Philippe AZULAY, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Nantes, Hopital Laennec Not yet recruiting
Nantes, France, 44093
Contact: Tiphaine ROUAUD, MD    +33 2 40 16 52 86    Tiphaine.Rouaud@chu-nantes.fr   
Principal Investigator: Tiphaine ROUAU, MD         
SERVICE DE NEUROLOGIE Centre Expert Parkinson Hopital de la Pitié-Salpêtrière Not yet recruiting
Paris, France, 75651
Contact: Jean-Christophe CORVOL, MD    +33 1 42 16 57 66    jean-christophe.corvol@aphp.fr   
Principal Investigator: Jean-Christophe CORVOL, MD         
Centre d'Inverstigation Clinique, CHU de Poitiers Not yet recruiting
Poitiers, France, 86021
Contact: Jean-Luc HOUETO, MD    +33 5 49 44 44 46    j.l.houeto@chu-poitiers.fr   
Principal Investigator: Jean-Luc HOUETO, MD         
SERVICE DE NEUROLOGIE, CHU de REIMS Not yet recruiting
Reims, France, 51100
Contact: Anne DOE DE MAINDREVILLE, MD       adoedemaindreville@chu-reims.fr   
Principal Investigator: Anne DOE DE MAINDREVILLE, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rennes, Hopital Pontchaillou Not yet recruiting
Rennes, France, 35033
Contact: Sophie DRAPIER, MD    +33 2 99 28 42 93    Sophie.Drapier@chu-rennes.fr   
Principal Investigator: Sophie DRAPIER, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rouen, Hopital Charles Nicolle Not yet recruiting
Rouen, France, 76031
Contact: David MALTETE, MD    +33 2 32 88 87 40    david.maltete@chu-rouen.fr   
Principal Investigator: David MALTETE, MD         
SERVICE DE NEUROLOGIE Unité de Mouvements Anormaux/Centre expert Parkinson, CHU de Strasbourg, Hopital de Hautepierre Recruiting
Strasbourg, France, 67098
Contact: Mathieu ANHEIM, MD    +33 3 88 12 85 35    mathieu.anheim@chru-strasbourg.fr   
Principal Investigator: Mathieu ANHEIM, MD         
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Toulouse, Hopital Pierre-Paul Riquet Not yet recruiting
Toulouse, France, 31059
Contact: Olivier RASCOL, MD    +33 5 61 14 59 62    olivier.rascol@univ-tlse3.fr   
Principal Investigator: Olivier RASCOL, MD         
Sponsors and Collaborators
University Hospital, Strasbourg, France
NS-PARK
EUCLID
F-CRIN
Investigators
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Principal Investigator: Mathieu ANHEIM, MD CHRU Strasbourg

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Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT03947216    
Other Study ID Numbers: 6398
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University Hospital, Strasbourg, France:
impulse control disorders
pimavanserin
Serotoninergic 5-HT2A inverse agonist
Dopamine agonist
Behavior
Additional relevant MeSH terms:
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Parkinson Disease
Disruptive, Impulse Control, and Conduct Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Mental Disorders
Pimavanserin
Antiparkinson Agents
Anti-Dyskinesia Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action