Perospirone

Last updated
Perospirone
Perospirone.svg
Perospirone-optimized-ball-and-stick.png
Clinical data
Trade names Lullan
AHFS/Drugs.com International Drug Names
Routes of
administration 		Oral
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
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]
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
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C23H30N4O2S
Molar mass 426.58 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+ Yes check.svgY
  • Key:GTAIPSDXDDTGBZ-OYRHEFFESA-N Yes check.svgY
 X mark.svgNYes check.svgY  (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]

Contents

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]

And the following with moderate affinity: [9]

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

See also

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Ziprasidone</span> Antipsychotic medication

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia, obsessive compulsive disorder (OCD), and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Sulpiride</span> Atypical antipsychotic

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purpose. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.

<span class="mw-page-title-main">Zotepine</span> Chemical compound

Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 and Japan since 1982.

<span class="mw-page-title-main">Paliperidone</span> Antipsychotic medication

Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Pimavanserin</span> Chemical compound

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

<span class="mw-page-title-main">Pomaglumetad</span> Drug, used as a treatment for schizophrenia

Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.

<span class="mw-page-title-main">Tiospirone</span> Pharmaceutical drug

Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class. It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects. However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone. It was found to be both more potent and more selective in comparison and was commercialized instead.

<span class="mw-page-title-main">Clocapramine</span> Chemical compound

Clocapramine, also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminostilbene class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

References

  1. 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. 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. 1 2 de Paulis T (January 2002). "Perospirone (Sumitomo Pharmaceuticals)". Current Opinion in Investigational Drugs. 3 (1): 121–129. PMID   12054062.
  4. 1 2 "Sumitomo Pharmaceuticals 2001 | News Release | Dainippon Sumitomo Pharma". Archived from the original on 24 February 2006.
  5. 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.
  6. 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.
  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. 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.
  10. ↑ Perospirone Hydrochloride. 23 September 2011. Retrieved 3 November 2013.{{cite book}}: |work= ignored (help)
  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. 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.
  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 from the original on 8 November 2013. Retrieved 3 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.

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