Perospirone
Chemical compound that acts as an atypical antipsychotic
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Trade names | Lullan |
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Protein binding | 92% [1] |
Metabolism | Hepatic [1] |
Elimination half-life | 1.9-2.5 hours [1] [2] |
Excretion | Renal (0.4% as unchanged drug) [1] |
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Chemical and physical data | |
Formula | C 23 H 30 N 4 O 2 S |
Molar mass | 426.58 g·mol −1 |
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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
Its primary uses are in the treatment of schizophrenia and bipolar mania. [3] [4]
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. [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
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 interval prolongation 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]
Discontinuation
The British 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
Perospirone binds to the following receptors with very high affinity (as an antagonist unless otherwise specified): [9] [16] [17] [18] [19] [20]
And the following receptor with high affinity: [9]
- H 1 (inverse agonist)
And the following with moderate affinity: [9]
And with low affinity for the following receptor: [9]
See also
- Azapirone
- Blonanserin — another second-generation antipsychotic that's only approved for clinical use in East Asia
- Mosapramine
- Zotepine
References
- 1 2 3 4 5 6 Onrust SV, McClellan K (2001). "Perospirone". CNS Drugs . 15 (4): 329–37, discussion 338. doi : 10.2165/00023210-200115040-00006 . PMID 11463136 .
- ↑ 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 .
- 1 2 de Paulis T (January 2002). "Perospirone (Sumitomo Pharmaceuticals)". Current Opinion in Investigational Drugs . 3 (1): 121–129. PMID 12054062 .
- 1 2 "Sumitomo Pharmaceuticals 2001 | News Release | Dainippon Sumitomo Pharma" . Archived from the original on 24 February 2006.
- 1 2 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.
- 1 2 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.
- ↑ 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 .
- ↑ 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 .
- 1 2 3 4 5 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 . S2CID 11543666 .
-
↑
Perospirone Hydrochloride
. 23 September 2011
. Retrieved
3 November
2013
.
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ignored ( help ) - ↑ 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 .
-
↑
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.
- 1 2 3 4 5 Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide . OUP Oxford. p. 207-216. ISBN 9780198527480 .
- ↑ 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 .
- ↑ Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013). Adherence to Antipsychotics in Schizophrenia . Springer Science & Business Media. p. 85. ISBN 9788847026797 .
- ↑ Roth, BL ; Driscol, J (12 January 2011). "PDSP K i Database" . Psychoactive Drug Screening Program (PDSP) . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013 . Retrieved 3 November 2013 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .