Risperidone

drugbox
IUPAC_name = 4- [2- [4-(6-fluorobenzo ["d"] isoxazol-3-yl)-
1-piperidyl] ethyl] -3-methyl-
2,6-diazabicyclo [4.4.0] deca-1,3-dien-5-one

---

CAS_number = 106266-06-2
ATC_prefix = N05
ATC_suffix = AX08
PubChem = 5073
DrugBank = APRD00187
C=23|H=27|F=1|N=4|O=2
molecular_weight = 410.485 g/mol
smiles = Fc1ccc2c(onc2C2CCN(CC2)CCc2c(C)nc3CCCCn3c2=O)c1
bioavailability = 70% (oral)
metabolism = Hepatic (CYP2D6-mediated)
elimination_half-life = 3–20 hours
excretion = Urinary
pregnancy_category = C
legal_status = Rx-only
routes_of_administration = Oral and extended-release intramuscular injection

Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the United Kingdom, Portugal and several other countries, Risperdal or Ridal in New Zealand, Rispolept in Eastern Europe, and Belivon, or Rispen elsewhere) is an atypical antipsychotic developed by Janssen-Cilag.

Uses

Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 [cite web
title =Electronic Orange Book
publisher =Food and Drug Administration
month=April | year=2007
url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020272&TABLE1=OB_Rx
accessdate =2007-05-24] for the treatment of schizophrenia. On Wednesday, August 22, 2007, Risperdal was approved as the only drug agent available for treatment of schizophrenia in children ages 13–18; it was also approved that same day for treatment of bipolar disorder in youths ages 10–18, joining lithium. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. In 2003 the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006 the FDA approved risperidone for the treatment of irritability in children and adolescents with autism. The FDA's decision was based in part on a study of autistic children with severe and enduring problems of tantrums, aggression, and self-injury; risperidone is not recommended for autistic children with mild aggression and explosive behavior without an enduring pattern. [cite journal |journal= J Autism Dev Disord |year=2008 |volume=38 |issue=6 |pages=1197–8 |title= How do I decide whether or not to use medication for my child with autism? should I try behavior therapy first? |author= Scahill L |doi=10.1007/s10803-008-0573-7 |pmid=18463973] Like other atypical antipsychotics, risperidone has also been used off-label for the treatment of anxiety disorders, such as obsessive-compulsive disorder; severe, treatment-resistant depression with or without psychotic features; Tourette syndrome; disruptive behavior disorders in children; and eating disorders, among others.cite press release
publisher=FDA
date=October 2 2006
url=http://www.fda.gov/bbs/topics/NEWS/2006/NEW01485.html
title=FDA Approves the First Drug to Treat Irritability Associated with Autism, Risperdal
accessdate=2006-10-02 ] In two small studies risperidone was reported to successfully treat the symptoms of phencyclidine psychosis due to acute intoxication [ AJ Giannini, GL Colapietro, DK Cook. Risperidone therapy in phencyclidine intoxication, Society for Neuroscience Abstracts. 22:77.12, 1996.] and chronic use . [ JF Gabbert,AJ Giannini. Dopaminergic/serotonergic actions of phencyclidine as a model for schizophrenia psychosis. American Journal of Therapeutics. 4:159-164, 1997. ]

A multi-year UK study by the Alzheimer's Research Trust suggested that this and other neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often made their condition worse. The study concluded that cquote|For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status and by some measures improved functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this possibility must be weighed against the unwanted effects of therapy. [cite journal
journal=PLOS Medicine
title= A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)
author= Ballard C, Lana MM, Theodoulou M "et al."
volume=5 |issue=4 |pages=e76
doi=10.1371/journal.pmed.0050076
pmid=18384230
url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050076
year=2008
laysummary=http://news.bbc.co.uk/1/hi/health/7319393.stm |laysource= BBC News |laydate=2008-04-01]

Patent status

Janssen's patent on Risperdal expired on December 29, 2007, opening the market for cheaper generic versions of the drug from other companies; however, Janssen had exclusive marketing rights until June 29, 2008, as the result of a pediatric extension.

Risperidone is available as a tablet in 0.25, 0.5, 1, 2, 3 and 4 mg sizes, and as a 25 mg, 37.5 mg and 50 mg ampoule Risperdal Consta, which is a depot injection administered once every two weeks. It is also available as a wafer known in the United States as Risperdal M-Tabs and elsewhere as Risperdal Quicklets.

ide effects

Common side effects include akathisia, anxiety, insomnia, low blood pressure, muscle stiffness, muscle pain, sedation, sexual dysfunction, tremors, increased salivation, and stuffy nose. Risperidone has been associated with minimal to moderate weight gain, with one study finding that 26 to 38 percent of participants on the drug experienced weight gain. [cite journal | author = Vanina "et al".
title = Body Weight Changes Associated With Psychopharmacology
journal = Psychiatric Services
volume = 53
pages = 842–847
month=July | year=2002
publisher = American Psychiatric Association
url=http://psychservices.psychiatryonline.org/cgi/content/full/53/7/842#SEC2 | doi = 10.1176/appi.ps.53.7.842
pmid = 12096167] [cite journal | author = Baldwin, D and Mayers, A.
title = Sexual side-effects of antidepressant and antipsychotic drugs
journal = Advances in Psychiatric Treatment
volume = 9
pages = 202–210
year=2003
publisher = Royal College of Psychiatrists
url=http://apt.rcpsych.org/cgi/content/full/9/3/202 | doi = 10.1192/apt.9.3.202 ]

Occasionally breast tenderness and eventually lactation in both genders may occur. Many antipsychotics are known to increase prolactin because they inhibit dopamine. However, risperidone is known to increase prolactin to a greater extent than most other antipsychotics, such as quetiapine. It is thought that once risperidone raises prolactin, it may cause non-cancerous tumors in the pituitary gland. This may recur even if the patient has switched to a different antipsychotic.cite journal | author=Szarfman A, Tonning J, Levine J, Doraiswamy P | title=Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. | journal=Pharmacotherapy | volume=26 | issue=6 | pages=748–58 | year=2006 | pmid=16716128 | doi=10.1592/phco.26.6.748]

Risperidone can potentially cause tardive dyskinesia (TD)cite web |url=http://www.risperdal.com/risperdal/shared/pi/risperdal.pdf |title=Risperdal: Full U.S. Prescribing Information |accessdate=2008-03-06 |format= |work= publisher=Ortho-McNeil-Janssen Pharmaceuticals] , extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).

Also, Risperidone can trigger diabetes and more serious conditions of glucose metabolism, including ketoacidosis and hyperosmolar coma.cite press release
publisher=FDA
date=April 19 2004
url=http://www.fda.gov/foi/warning_letters/archive/g4628d.htm
title=FDA Warning Letter
accessdate=2007-05-02 ]

Pharmacology

This drug belongs to a class of Anti-psychotic drugs known as Atypical Neuroleptics. It is a strong dopamine antagonist. It has a high affinity for D₂ dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT_2C, linked to weight gain, 5-HT_2A,linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the Typical Neuroleptics through action at 5-HT_1A. The latter action may lead to an increased release of Dopamine from Mesocortical neurones in the brain.

It reaches peak plasma levels quickly regardless of whether it is administered as a liquid or pill. Risperidone is metabolised fairly quickly, so this potential for nausea subsides usually in two to three hours. However the active metabolite, 9-hydroxy-risperidone, which has similar pharmacodynamics to risperidone, lingers in the body for much longer, and has been developed as a antipsychotic in its own right, called Paliperidone.

An intramuscular preparation, marketed as Risperdal Consta, can be given once every two weeks. It is slowly released from the injection site. It can be useful in patients who have difficulty taking oral medication for any reason. Some people prefer a once-every-two-weeks injection to daily pills. It also helps the physician ensure compliance. Doses range from 25 to 50 mg given as an intramuscular injection once every two weeks.

References

External links

* [http://www.drugs.com/pdr/risperidone.html Drugs.com Professional information on risperidone]
* [http://www.drugs.com/mtm/risperidone.html Drugs.com Consumer information on risperidone]
* [http://www.risperdal.com/ Janssen L.P. official web site on Risperdal (risperidone)]
* [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=475100 PubChem Substance Summary: Risperidone] National Center for Biotechnology Information.