Perospirone

Overview

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.[1][2][3] WP

Uses, dosage and effects

Medical uses

Its primary uses are in the treatment of schizophrenia and bipolar mania.[2][3] WP

Schizophrenia

In a clinical trial that compared it to haloperidol in the treatment of schizophrenia it was found to produce significantly superior overall symptom control. In another clinical trial perospirone was compared with mosapramine and produced a similar reduction in total PANSS score, except with respect to the blunted affect part of the PANSS negative score, in which perospirone produced a significantly greater improvement. In an open-label clinical trial comparing aripiprazole with perospirone there was no significant difference between the two treatments discovered in terms of both efficacy and tolerability. In 2009 a clinical trial found that perospirone produced a similar reduction of PANSS score than risperidone and the extrapyramidal side effects was similar in both frequency and severity between groups.[4–7] WP

A meta-analysis published in 2013 found that it is statistically significantly less efficacious than other second-generation antipsychotics.[8] WP

Risks and side effects

Adverse effects

Has a higher incidence of extrapyramidal side effects than the other atypical antipsychotics, but still less than that seen with typical antipsychotics. 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. It may produce less QT interval prolongation than zotepine, as in one patient who had previously been on zotepine switching to perospirone corrected their prolonged QT interval. It also tended to produce less severe extrapyramidal side effects than haloperidol in a clinical trial comparing the two (although statistical significance was not reached).[1][4][5][9][10] WP

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a felling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.[11][12] WP

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.[12][13][14] WP

Pharmacology

Pharmacology

Perospirone binds to the following receptors with very high affinity (as an antagonist unless otherwise specified):[8][15–19] WP

• 5-HT1A (partial agonist; Kᵢ = 2.9 nM)[8][15–19] WP
• 5-HT2A (inverse agonist; Kᵢ = 1.3 nM)[8][15–19] WP
• D₂ (Kᵢ = 0.6 nM)[8][15–19] WP

And the following receptor with high affinity:[8] WP

• H₁ (inverse agonist)[8] WP

And the following with moderate affinity:[8] WP

• α₁ adrenoceptor[8] WP

And with low affinity for the following receptor:[8] WP

Chemistry

Formula

C23H30N4O2S PC

CAS number

150915-41-6 PC

Molar mass (g/mol)

426.6 PC

IUPAC name (computed by PubChem)

(3aR,7aS)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione PC

SMILES

C1CC[C@H]2[C@@H](C1)C(=O)N(C2=O)CCCCN3CCN(CC3)C4=NSC5=CC=CC=C54 PC

InChIKey

FBVFZWUMDDXLLG-HDICACEKSA-N PC

PubChem CID

115368

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Onrust SV, McClellan K. Perospirone. CNS Drugs. 2001. doi:10.2165/00023210-200115040-00006 · PMID 11463136
2. Journal / agency de Paulis T. Perospirone (Sumitomo Pharmaceuticals). Current Opinion in Investigational Drugs. January 2002. PMID 12054062
3. Other Now on the Market: New Antipsychotic "Lullan® Tablets" - serotonin-dopamine antagonist originated in Japan. 8 February 2001
4. Journal / agency Murasaki M, Koyama T, Machiyama Y. Clinical evaluation of a new antipsychotic, perospirone HCl, on schizophrenia: a comparative double-blind study with haloperidol. Rinsho Hyoka. 1997
5. Journal / agency Kudo Y, Nakajima T, Saito M. 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. 1997
6. Journal / agency Takekita Y, Kato M, Wakeno M, Sakai S, Suwa A, Nishida K, Okugawa G, Kinoshita T. A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry. January 2013. doi:10.1016/j.pnpbp.2012.09.010 · PMID 23022672
7. Journal / agency Okugawa G, Kato M, Wakeno M, Koh J, Morikawa M, Matsumoto N, Shinosaki K, Yoneda H, Kishimoto T, Kinoshita T. Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study. Psychiatry and Clinical Neurosciences. June 2009. doi:10.1111/j.1440-1819.2009.01947.x · PMID 19566763
8. Journal / agency Kishi T, Iwata N. Efficacy and tolerability of perospirone in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. CNS Drugs. September 2013. doi:10.1007/s40263-013-0085-7 · PMID 23812802
9. Other Martindale: The Complete Drug Reference. 23 September 2011
10. Journal / agency Suzuki Y, Watanabe J, Sugai T, Fukui N, Ono S, Tsuneyama N, Saito M, Someya T. Improvement in QTc prolongation induced by zotepine following a switch to perospirone. Psychiatry and Clinical Neurosciences. April 2012. doi:10.1111/j.1440-1819.2012.02321.x · PMID 22443250
11. Other British National Formulary. March 2009
12. Other Haddad PM, Dursun S, Deakin B. Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. 2004
13. Journal / agency Moncrieff J. Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatrica Scandinavica. July 2006. doi:10.1111/j.1600-0447.2006.00787.x · PMID 16774655
14. Other Sacchetti E, Vita A, Siracusano A, Fleischhacker W. Adherence to Antipsychotics in Schizophrenia. 2013
15. Other Roth BL, Driscol, J. PDSP Kᵢ Database. 12 January 2011
16. Journal / agency Hirose A, Kato T, Ohno Y, Shimizu H, Tanaka H, Nakamura M, Katsube J. Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5-hydroxytryptamine2 and dopamine2 antagonistic actions. Japanese Journal of Pharmacology. July 1990. doi:10.1254/jjp.53.321 · PMID 1975278
17. Journal / agency Kato T, Hirose A, Ohno Y, Shimizu H, Tanaka H, Nakamura M. Binding profile of SM-9018, a novel antipsychotic candidate. Japanese Journal of Pharmacology. December 1990. doi:10.1254/jjp.54.478 · PMID 1982326
18. Journal / agency Odagaki Y, Toyoshima R. 5-HT1A receptor agonist properties of antipsychotics determined by [35S]GTPgammaS binding in rat hippocampal membranes. Clinical and Experimental Pharmacology & Physiology. 2007. doi:10.1111/j.1440-1681.2007.04595.x · PMID 17439416
19. Journal / agency Seeman P, Tallerico T. 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. March 1998. doi:10.1038/sj.mp.4000336 · PMID 9577836

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