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Perospirone

From Wikipedia, the free encyclopedia
Atypical antipsychotic medication
Pharmaceutical compound
Perospirone
Clinical data
Trade namesLullan
AHFS/Drugs.comInternational Drug Names
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding92%[1]
MetabolismHepatic[1]
Eliminationhalf-life1.9–2.5 hours[1][2]
ExcretionRenal (0.4% as unchanged drug)[1]
Identifiers
  • (3aS,7aR)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
CAS Number
PubChemCID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC23H30N4O2S
Molar mass426.58 g·mol−1
3D model (JSmol)
  • O=C4N(CCCCN1CCN(CC1)C\3=N\SCc2ccccc2/3)C(=O)[C@@H]5CCCC[C@H]45
  • InChI=1S/C24H32N4O2S/c29-23-20-9-3-4-10-21(20)24(30)28(23)12-6-5-11-26-13-15-27(16-14-26)22-19-8-2-1-7-18(19)17-31-25-22/h1-2,7-8,20-21H,3-6,9-17H2/t20-,21+ checkY
  • Key:GTAIPSDXDDTGBZ-OYRHEFFESA-N checkY
 ☒NcheckY (what is this?)  (verify)

Perospirone (Lullan) is anatypical antipsychotic of theazapirone family.[1] It was introduced inJapan byDainippon Sumitomo Pharma in 2001 for the treatment ofschizophrenia and acute cases ofbipolarmania.[3][4]

Medical uses

[edit]

Its primary uses are in the treatment of schizophrenia and bipolar mania.[3][4]

Schizophrenia

[edit]

In a clinical trial that compared it tohaloperidol in the treatment of schizophrenia it was found to produce significantly superior overall symptom control.[5] In another clinical trial perospirone was compared withmosapramine and produced a similar reduction in totalPANSS score, except with respect to the blunted affect part of the PANSS negative score, in which perospirone produced a significantly greater improvement.[6] In an open-label clinical trial comparingaripiprazole with perospirone there was no significant difference between the two treatments discovered in terms of both efficacy and tolerability.[7] In 2009 a clinical trial found that perospirone produced a similar reduction of PANSS score thanrisperidone and the extrapyramidal side effects was similar in both frequency and severity between groups.[8]

A meta-analysis published in 2013 found that it is statistically significantly less efficacious than other second-generation antipsychotics.[9]

Adverse effects

[edit]

Has a higher incidence of extrapyramidal side effects than the other atypical antipsychotics, but still less than that seen with typical antipsychotics.[1][10] A trend was observed in a clinical trial comparing mosapramine with perospirone that favoured perospirone for producing less prominent extrapyramidal side effects than mosapramine although statistical significant was not reached.[6] It may produce lessQT interval prolongation thanzotepine, as in one patient who had previously been on zotepine switching to perospirone corrected their prolonged QT interval.[11] It also tended to produce less severeextrapyramidal side effects than haloperidol in a clinical trial comparing the two (although statistical significance was not reached).[5]

Discontinuation

[edit]

TheBritish National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[12] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[13] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[13] Less commonly there may be a felling of the world spinning, numbness, or muscle pains.[13] Symptoms generally resolve after a short period of time.[13]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[14] It may also result in reoccurrence of the condition that is being treated.[15] Rarely tardive dyskinesia can occur when the medication is stopped.[13]

Pharmacology

[edit]

Perospirone binds to the following receptors with very high affinity (as an antagonist unless otherwise specified):[9][16][17][18][19][20]

  • 5-HT1A (partial agonist; Ki = 2.9 nM)
  • 5-HT2A (inverse agonist; Ki = 1.3 nM)
  • D2 (Ki = 0.6 nM)

And the following receptor with high affinity:[9]

  • H1 (inverse agonist)

And the following with moderate affinity:[9]

And with low affinity for the following receptor:[9]

See also

[edit]

References

[edit]
  1. ^abcdefOnrust SV, McClellan K (2001). "Perospirone".CNS Drugs.15 (4):329–37, discussion 338.doi:10.2165/00023210-200115040-00006.PMID 11463136.S2CID 262520276.
  2. ^Yasui-Furukori N, Furukori H, Nakagami T, Saito M, Inoue Y, Kaneko S, Tateishi T (August 2004). "Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response".Therapeutic Drug Monitoring.26 (4):361–365.doi:10.1097/00007691-200408000-00004.PMID 15257064.S2CID 43362616.
  3. ^abde Paulis T (January 2002). "Perospirone (Sumitomo Pharmaceuticals)".Current Opinion in Investigational Drugs.3 (1):121–129.PMID 12054062.
  4. ^ab"Now on the Market : New Antipsychotic "Lullan® Tablets" - serotonin-dopamine antagonist originated in Japan".Sumitomo Pharmaceuticals 2001 | News Release | Dainippon Sumitomo Pharma. 8 February 2001. Archived fromthe original on 24 February 2006.
  5. ^abMurasaki M, Koyama T, Machiyama Y, et al. (1997). "Clinical evaluation of a new antipsychotic, perospirone HCl, on schizophrenia: a comparative double-blind study with haloperidol".Rinsho Hyoka.24 (2–3):159–205.
  6. ^abKudo Y, Nakajima T, Saito M, et al. (1997). "Clinical evaluation of a serotonin-2 and dopamine-2 receptor antagonist (SDA), perospirone HCl on schizophrenia: a comparative double-blind study with mosapramine HCl".Rinsho Hyoka.24 (2–3):207–48.
  7. ^Takekita Y, Kato M, Wakeno M, Sakai S, Suwa A, Nishida K, et al. (January 2013). "A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients".Progress in Neuro-Psychopharmacology & Biological Psychiatry.40:110–114.doi:10.1016/j.pnpbp.2012.09.010.PMID 23022672.S2CID 10315774.
  8. ^Okugawa G, Kato M, Wakeno M, Koh J, Morikawa M, Matsumoto N, et al. (June 2009)."Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study".Psychiatry and Clinical Neurosciences.63 (3):322–328.doi:10.1111/j.1440-1819.2009.01947.x.PMID 19566763.S2CID 23636639.
  9. ^abcdeKishi T, Iwata N (September 2013). "Efficacy and tolerability of perospirone in schizophrenia: a systematic review and meta-analysis of randomized controlled trials".CNS Drugs.27 (9):731–741.doi:10.1007/s40263-013-0085-7.PMID 23812802.S2CID 11543666.
  10. ^"Perospirone Hydrochloride".Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 23 September 2011. Retrieved3 November 2013.
  11. ^Suzuki Y, Watanabe J, Sugai T, Fukui N, Ono S, Tsuneyama N, et al. (April 2012). "Improvement in QTc prolongation induced by zotepine following a switch to perospirone".Psychiatry and Clinical Neurosciences.66 (3): 244.doi:10.1111/j.1440-1819.2012.02321.x.PMID 22443250.S2CID 32269750.
  12. ^Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1".British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192.ISBN 978-0-85369-845-6.Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
  13. ^abcdeHaddad PM, Dursun S, Deakin B (2004).Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. p. 207-216.ISBN 9780198527480.
  14. ^Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse".Acta Psychiatrica Scandinavica.114 (1):3–13.doi:10.1111/j.1600-0447.2006.00787.x.PMID 16774655.S2CID 6267180.
  15. ^Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013).Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85.ISBN 9788847026797.
  16. ^Roth BL, Driscol, J (12 January 2011)."PDSP Ki Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived fromthe original on 8 November 2013. Retrieved3 November 2013.
  17. ^Hirose A, Kato T, Ohno Y, Shimizu H, Tanaka H, Nakamura M, Katsube J (July 1990)."Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5-hydroxytryptamine2 and dopamine2 antagonistic actions".Japanese Journal of Pharmacology.53 (3):321–329.doi:10.1254/jjp.53.321.PMID 1975278.
  18. ^Kato T, Hirose A, Ohno Y, Shimizu H, Tanaka H, Nakamura M (December 1990)."Binding profile of SM-9018, a novel antipsychotic candidate".Japanese Journal of Pharmacology.54 (4):478–481.doi:10.1254/jjp.54.478.PMID 1982326.
  19. ^Odagaki Y, Toyoshima R (2007). "5-HT1A receptor agonist properties of antipsychotics determined by [35S]GTPgammaS binding in rat hippocampal membranes".Clinical and Experimental Pharmacology & Physiology.34 (5–6):462–466.doi:10.1111/j.1440-1681.2007.04595.x.PMID 17439416.S2CID 22450517.
  20. ^Seeman P, Tallerico T (March 1998). "Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors".Molecular Psychiatry.3 (2):123–134.doi:10.1038/sj.mp.4000336.PMID 9577836.S2CID 16484752.
Typical
Disputed
Atypical
Others
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
H1
Agonists
Antagonists
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7

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