Perospirone

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Perospirone
Perospirone2DACS2.svg
Perospirone3Dan.gif
Systematic (IUPAC) name
(3aR,7aS)-2-{4-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]butyl}hexahydro-1H-isoindole-1,3(2H)-dione
Clinical data
Trade names Lullan
AHFS/Drugs.com International Drug Names
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Protein binding 92%[1]
Metabolism Hepatic[1]
Half-life 1.9-2.5 hours[1][2]
Excretion Renal (0.4% as unchanged drug)[1]
Identifiers
CAS number 150915-41-6 N
ATC code None
PubChem CID 115368
ChemSpider 16737064 YesY
UNII N303OK87DT YesY
Chemical data
Formula C23H30N4O2S 
Mol. mass 426.57 g/mol
 N (what is this?)  (verify)

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family.[1] It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.[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 to haloperidol in the treatment of schizophrenia it was found to produce significantly superior overall symptom control.[5] 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.[6] 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.[7] 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.[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 less QT intervalprolongation than zotepine, 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 severe extrapyramidal side effects than haloperidol in a clinical trial comparing the two (although statistical significance was not reached).[5]

Pharmacology[edit]

Perospirone binds to the following receptors with very high affinity (as an antagonist unless otherwise specified):[12][9][13][12][14][15][16]

  • 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. ^ a b c d e f Onrust, SV; McClellan, K (2001). "Perospirone". CNS Drugs 15 (4): 329–37; discussion 338. doi:10.2165/00023210-200115040-00006. PMID 11463136. 
  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". Therapeutic Drug Monitoring 26 (4): 361–365. doi:10.1097/00007691-200408000-00004. PMID 15257064. 
  3. ^ a b de Paulis, T (January 2002). "Perospirone (Sumitomo Pharmaceuticals)". Current Opinion in Investigational Drugs 3 (1): 121–9. PMID 12054062. 
  4. ^ a b "Sumitomo Pharmaceuticals 2001 | News Release | Dainippon Sumitomo Pharma". 
  5. ^ a b Murasaki, 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. ^ a b Kudo, 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; Okugawa, G; Kinoshita, T (January 2013). "A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients". Progress in Neuro-Psychopharmacology and Biological Psychiatry 40: 110–114. doi:10.1016/j.pnpbp.2012.09.010. PMID 23022672. 
  8. ^ Okugawa, G; Kato, M; Wakeno, M; Koh, J; Morikawa, M; Matsumoto, N; Shinosaki, K; Yoneda, H; Kishimoto, T; Kinoshita, T (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. 
  9. ^ a b c d e Kishi, 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. 
  10. ^ "Perospirone Hydrochloride". Martindale: The Complete Drug Reference (The Royal Pharmaceutical Society of Great Britain). 23 September 2011. Retrieved 3 November 2013. 
  11. ^ Suzuki, Y; Watanabe, J; Sugai, T; Fukui, N; Ono, S; Tsuneyama, N; Saito, M; Someya T (March 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. 
  12. ^ a b 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): 321–9. doi:10.1254/jjp.53.321. PMID 1975278. 
  13. ^ 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. Retrieved 3 November 2013. 
  14. ^ 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): 478–81. doi:10.1254/jjp.54.478. PMID 1982326. 
  15. ^ 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): 462–6. doi:10.1111/j.1440-1681.2007.04595.x. PMID 17439416. 
  16. ^ 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): 123–34. doi:10.1038/sj.mp.4000336. PMID 9577836.