Page last updated: 2024-11-07

perospirone

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Perospirone is a novel atypical antipsychotic with high affinity for 5-HT1A and 5-HT2A receptors. It is currently in clinical trials for the treatment of schizophrenia and other psychiatric disorders. Research into its synthesis and pharmacological effects is ongoing, with particular interest in its potential for improved efficacy and tolerability compared to existing antipsychotics.'

perospirone: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID115368
CHEMBL ID1472975
CHEBI ID94777
SCHEMBL ID120579
MeSH IDM0180187

Synonyms (37)

Synonym
lullan
perospirone
perospirone [inn]
(3ar,7as)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
A809087
CHEMBL1472975
(3ar,7as)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione;perospirone
150915-41-6
1h-isoindole-1,3(2h)-dione, 2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)hexahydro-, (3ar,7as)-rel-
unii-n303ok87dt
cis-n-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-1,2-cyclohexanedicarboximide
1h-isoindole-1,3(2h)-dione, 2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)hexahydro-, cis-
n303ok87dt ,
perospirone [who-dd]
perospirone [mi]
S5185
AKOS025311209
CCG-221234
(3as,7ar)-2-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
lullan (japan)
gtpl7556
AB00698486-07
SCHEMBL120579
DTXSID2048163
DB08922
CHEBI:94777
(3ar,7as)-2-[4-[4-(1,2-benzothiazol-3-yl)-1-piperazinyl]butyl]-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
cis-n-[4-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide
J-008757
MRF-0000147
HMS3715H10
(3ar,7as)-2-(4-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)butyl)hexahydro-1h-isoindole-1,3(2h)-dione
HY-B0731A
AS-14845
Q6590349
CS-0019906
perospirine

Research Excerpts

Overview

Perospirone is a second-generation antipsychotic (SGA) used only in Japan. It acts as a serotonin (5-HT)1A receptor partial agonist, 5-HT2A receptor inverse agonist and dopamine (D)₂, D₄, and α₁-adrenergic receptor antagonist.

ExcerptReferenceRelevance
"Perospirone is a second-generation antipsychotic (SGA) used only in Japan, and acts as a serotonin (5-HT)1A receptor partial agonist, 5-HT2A receptor inverse agonist, and dopamine (D)₂, D₄, and α₁-adrenergic receptor antagonist. "( Efficacy and tolerability of perospirone in schizophrenia: a systematic review and meta-analysis of randomized controlled trials.
Iwata, N; Kishi, T, 2013
)
2.12
"Perospirone is a novel second-generation antipsychotic drug with high affinity to dopamine D(2) receptor and short half-life of plasma concentration. "( Dopamine D2 receptor occupancy by perospirone: a positron emission tomography study in patients with schizophrenia and healthy subjects.
Arakawa, R; Ito, H; Okubo, Y; Okumura, M; Suhara, T; Takahashi, H; Takano, A; Takano, H, 2010
)
2.08
"Perospirone is a novel serotonin-2 and dopamine-2 receptor antagonist (SDA) developed in Japan. "( [Perospirone therapy in elderly patients with schizophrenia].
Honma, H; Iwasaki, S; Kondo, C; Masui, T; Matsubara, S; Osawa, T, 2003
)
2.67
"Perospirone is a new antipsychotic drug in which dopamine D(2) antagonist and serotonin 5-HT(2) antagonist effects have been found in animal studies. "( A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic effects in human brain: findings from neuroendocrine challenge tests.
Inoue, Y; Iwakawa, M; Kojima, H; Nakamura, J; Soya, A; Terao, T; Ueda, N; Yoshimura, R, 2004
)
2.08
"Perospirone is a novel atypical antipsychotic with a unique combination of 5-HT1A receptor agonism as well as 5-HT2A and D2 receptor antagonism. "( Perospirone, a novel atypical antipsychotic drug, potentiates fluoxetine-induced increases in dopamine levels via multireceptor actions in the rat medial prefrontal cortex.
Katoh, S; Nisijima, K; Shioda, K; Yoshino, T; Yui, K, 2004
)
3.21
"Perospirone is a serotonin-dopamine antagonist (SDA) recently developed in Japan as an atypical antipsychotic to be used in the treatment of schizophrenia. "( Effects of serotonin-dopamine antagonists on prepulse inhibition and neurotransmitter contents in the rat cortex.
Ito, C; Ojima, T; Sakurai, E; Watanabe, T; Yanai, K, 2004
)
1.77
"Perospirone is a novel atypical antipsychotic drug with dopamine (DA) D(2)- and serotonin (5-hydroxytryptamine, 5-HT) 5-HT(2A)-receptor antagonist, and 5-HT(1A)-receptor agonist properties. "( Perospirone, a novel antipsychotic drug, inhibits marble-burying behavior via 5-HT1A receptor in mice: implications for obsessive-compulsive disorder.
Egashira, N; Fujiwara, M; Harada, S; Iwasaki, K; Matsushita, M; Mishima, K; Nishimura, R; Okuno, R, 2005
)
3.21
"Perospirone is an atypical antipsychotic agent originated and clinically used in Japan. "( Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone.
Koyama, T; Kusumi, I; Masui, T; Takahashi, Y, 2006
)
2.01
"Perospirone is a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist which originated in Japan. "( Effect of carbamazepine on the single oral dose pharmacokinetics of perospirone and its active metabolite.
Koyama, T; Kusumi, I; Masui, T; Takahashi, Y, 2006
)
2.01
"Perospirone is a novel atypical antipsychotic with a unique combination of 5-HT(1A) receptor agonism as well as 5-HT(2A) and D(2) receptor antagonism. "( Determination of perospirone by liquid chromatography/electrospray mass spectrometry: application to a pharmacokinetic study in healthy Chinese volunteers.
Li, HD; Liu, WY; Ma, N; Wang, F; Xiang, DX; Zhang, BK; Zhu, RH; Zhu, YG, 2007
)
2.12
"Perospirone is a second-generation antipsychotic agent with antagonist effects on both serotonin 5-HT(2A) and dopamine D(2) receptors, as well as a unique agonist effects on serotonin 5-HT(1A) receptors."( Perospirone augmentation of paroxetine in treatment of refractory obsessive-compulsive disorder with depression.
Hirayasu, Y; Karashima, A; Otsuka, T; Shioya, H; Sugiyama, N; Togo, T; Uehara, K; Yoshimi, A, 2007
)
2.5
"Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity. "( Perospirone in the treatment of patients with delirium.
Atsuta, H; Furuta, K; Hirasawa, T; Masaki, H; Nishikawa, T; Takeuchi, T; Yukizane, T, 2007
)
3.23
"Perospirone (PER) is a novel atypical antipsychotic drug for the treatment of schizophrenia and other psychotic disorders. "( Effect of the novel antipsychotic drug perospirone on P-glycoprotein function and expression in Caco-2 cells.
Li, HD; Li, KY; Zhou, YG, 2008
)
2.06
"Perospirone is an atypical antipsychotic agent for the treatment of schizophrenia. "( Perospirone.
McClellan, K; Onrust, SV, 2001
)
3.2
"Perospirone is a serotonin 5-HT2 antagonist and dopamine D2 antagonist developed by Sumitomo Pharmaceuticals for the potential treatment of schizophrenia and other psychoses [381769]. "( Perospirone (Sumitomo Pharmaceuticals).
de Paulis, T, 2002
)
3.2

Effects

ExcerptReferenceRelevance
"Perospirone has a uniquely high affinity for serotonin-1A receptors, and it could be speculated that perospirone, as a serotonin-1A receptor agonist combined with SDA, may have greater efficacy for treatment-refractory symptoms of schizophrenia."( Effective treatment of coprophagia in a patient with schizophrenia with the novel atypical antipsychotic drug perospirone.
Harada, KI; Saito, T; Yamamoto, K, 2006
)
1.27
"Perospirone has a uniquely high affinity for serotonin-1A receptors, and it could be speculated that perospirone, as a serotonin-1A receptor agonist combined with SDA, may have greater efficacy for treatment-refractory symptoms of schizophrenia."( Effective treatment of coprophagia in a patient with schizophrenia with the novel atypical antipsychotic drug perospirone.
Harada, KI; Saito, T; Yamamoto, K, 2006
)
1.27

Actions

ExcerptReferenceRelevance
"Perospirone also had lower scores related to extrapyramidal symptoms than other pooled antipsychotics (SMD = -0.30, p = 0.01)."( Efficacy and tolerability of perospirone in schizophrenia: a systematic review and meta-analysis of randomized controlled trials.
Iwata, N; Kishi, T, 2013
)
1.4

Toxicity

ExcerptReferenceRelevance
" The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety."( Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings.
Inoue, S; Maeda, I; Ogawa, A; Terada, S; Yamada, N; Yoshiuchi, K, 2022
)
1.02

Pharmacokinetics

Aripiprazole, perospirone, lurasidone and cariprazine share some of the pharmacokinetic characteristics of older, lipophilic antipsychotics. Each has some distinct pharmacokinetics features that are clinically beneficial and some that are not.

ExcerptReferenceRelevance
" The following pharmacokinetic parameters were elucidated after administering a single dose of 8mg perospirone hydrochloride."( Determination of perospirone by liquid chromatography/electrospray mass spectrometry: application to a pharmacokinetic study in healthy Chinese volunteers.
Li, HD; Liu, WY; Ma, N; Wang, F; Xiang, DX; Zhang, BK; Zhu, RH; Zhu, YG, 2007
)
0.9
"23) L/h, respectively; peak plasma concentration Cmax were (8."( Determination of azelnidipine by LC-ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers.
Fan, HW; Hu, Q; Ji, HJ; Xiao, DW; Zhou, XH; Zhu, YB; Zou, JJ, 2008
)
0.35
" The author provides the reader with knowledge of the fundamental pharmacokinetic characteristics and metabolic pathways of these new antipsychotics, emphasizing the clinically important common features and differences compared to other older agents."( Pharmacokinetics and metabolism update for some recent antipsychotics.
Caccia, S, 2011
)
0.37
"Aripiprazole, perospirone, lurasidone and cariprazine share some of the pharmacokinetic characteristics of older, lipophilic antipsychotics and, like these, each has some distinct pharmacokinetic features that are clinically beneficial and some that are not."( Pharmacokinetics and metabolism update for some recent antipsychotics.
Caccia, S, 2011
)
0.73

Compound-Compound Interactions

ExcerptReferenceRelevance
"In vitro metabolism studies were conducted to assess drug-drug interactions between perospirone, an antipsychotic agent, and concomitantly administered drugs--biperiden, flunitrazepam, haloperidol, and diazepam--using human liver microsomes."( In vitro drug-drug interactions with perospirone and concomitantly administered drugs in human liver microsomes.
Kanamaru, H; Komuro, S; Mizuno, Y; Shimakura, J; Tani, N,
)
0.63

Dosage Studied

The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed. Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perOSPirone in females.

ExcerptRelevanceReference
"), all reduced the freezing behavior with U-shaped dose-response curves."( Evaluation of perospirone (SM-9018), a novel serotonin-2 and dopamine-2 receptor antagonist, and other antipsychotics in the conditioned fear stress-induced freezing behavior model in rats.
Ishibashi, T; Ishida-Tokuda, K; Morita, T; Nakamura, M; Ohno, Y; Sakamoto, H; Tojima, R; Wakabayashi, J, 1996
)
0.65
" Changes in prolactin concentration from 1 to 2 hours after the dosing were parallel with drug concentrations, and almost normal ranges of prolactin concentration were observed before the morning dose despite steady state."( Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response.
Furukori, H; Inoue, Y; Kaneko, S; Nakagami, T; Saito, M; Tateishi, T; Yasui-Furukori, N, 2004
)
0.57
" Plasma concentrations of perospirone and ID-15036 up to 10 hours after perospirone dosing were measured by high-performance liquid chromatography (HPLC)."( Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone.
Koyama, T; Kusumi, I; Masui, T; Takahashi, Y, 2006
)
0.87
"5 hours after dosing and approximately 60 ng/mL 18 hours after dosing, when consciousness became clear."( [Pharmacokinetics of perospirone hydrochloride at an excessive dose and changes in the serum prolactin level].
Ishii, E; Ishimatsu, S; Kizu, J; Otani, N; Tsuchiya, M, 2007
)
0.66
" The mean level of perospirone at 11-15 h after a last dosing was much lower (0."( Long-term perospirone treatment with a single dose at bedtime in schizophrenia: relevant to intermittent dopamine D2 receptor antagonism.
Koyama, T; Kusumi, I; Masui, T, 2008
)
1.08
" This single dosage may be sufficient for the treatment of schizophrenia and might be useful as a new dosing schedule choice."( Dopamine D2 receptor occupancy by perospirone: a positron emission tomography study in patients with schizophrenia and healthy subjects.
Arakawa, R; Ito, H; Okubo, Y; Okumura, M; Suhara, T; Takahashi, H; Takano, A; Takano, H, 2010
)
0.64
" The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D(2) blockade, in psychiatric patients treated with perospirone."( The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients.
Fukui, N; Inoue, Y; Ono, S; Sawamura, K; Someya, T; Sugai, T; Suzuki, Y; Tsuneyama, N; Watanabe, J, 2010
)
0.91
"The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p=0."( The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients.
Fukui, N; Inoue, Y; Ono, S; Sawamura, K; Someya, T; Sugai, T; Suzuki, Y; Tsuneyama, N; Watanabe, J, 2010
)
0.92
" Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perospirone in females."( Prolactin fluctuation over the course of a day during treatments with three atypical antipsychotics in schizophrenic patients.
Fujii, A; Furukori, H; Inoue, Y; Kaneko, S; Sugawara, N; Tsuchimine, S; Yasui-Furukori, N, 2010
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
N-arylpiperazine
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (4)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency44.66840.354828.065989.1251AID504847
gemininHomo sapiens (human)Potency11.88560.004611.374133.4983AID624296
peripheral myelin protein 22Rattus norvegicus (Norway rat)Potency6.42410.005612.367736.1254AID624032
lamin isoform A-delta10Homo sapiens (human)Potency12.58930.891312.067628.1838AID1487
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID1345788Human D2 receptor (Dopamine receptors)1975Proceedings of the National Academy of Sciences of the United States of America, Nov, Volume: 72, Issue:11
Brain receptors for antipsychotic drugs and dopamine: direct binding assays.
AID1346919Rat 5-HT2A receptor (5-Hydroxytryptamine receptors)1975Proceedings of the National Academy of Sciences of the United States of America, Nov, Volume: 72, Issue:11
Brain receptors for antipsychotic drugs and dopamine: direct binding assays.
AID1345814Human D4 receptor (Dopamine receptors)1998Molecular psychiatry, Mar, Volume: 3, Issue:2
Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors.
AID1345833Human D3 receptor (Dopamine receptors)1992European journal of pharmacology, Apr-10, Volume: 225, Issue:4
Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (104)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901 (0.96)18.7374
1990's21 (20.19)18.2507
2000's53 (50.96)29.6817
2010's23 (22.12)24.3611
2020's6 (5.77)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 34.25

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index34.25 (24.57)
Research Supply Index4.91 (2.92)
Research Growth Index6.09 (4.65)
Search Engine Demand Index42.91 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (34.25)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials24 (21.62%)5.53%
Reviews10 (9.01%)6.00%
Case Studies22 (19.82%)4.05%
Observational1 (0.90%)0.25%
Other54 (48.65%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Objective to Evaluate the Efficacy and Safety of Peropirone Hydrochloride Tablets in the Treatment of Adolescent Bipolar Depressive Episode: a Multicenter Open Randomized Controlled Clinical Trial [NCT04826510]Phase 4189 participants (Anticipated)Interventional2020-11-25Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]