Spiperone

Spiperone
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	Rx-only (JP);
Pharmacokinetic data
Metabolism	Hepatic
Excretion	Renal
Identifiers
	IUPAC name 8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;
CAS Number	749-02-0 ;
PubChem CID	5265;
IUPHAR/BPS	99;
ChemSpider	5075 ;
UNII	4X6E73CJ0Q;
KEGG	D01051 ;
ChEBI	CHEBI:9233 ;
ChEMBL	ChEMBL267930 ;
CompTox Dashboard (EPA)	DTXSID5045205 ;
ECHA InfoCard	100.010.931
Chemical and physical data
Formula	C23H26FN3O2
Molar mass	395.478 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c1ccc(cc1)N2CNC(=O)C23CCN(CC3)CCCC(=O)c4ccc(cc4)F;
	InChI InChI=1S/C23H26FN3O2/c24-19-10-8-18(9-11-19)21(28)7-4-14-26-15-12-23(13-16-26)22(29)25-17-27(23)20-5-2-1-3-6-20/h1-3,5-6,8-11H,4,7,12-17H2,(H,25,29) ; Key:DKGZKTPJOSAWFA-UHFFFAOYSA-N ;
	(verify)

Spiperone (Spiroperidol; brand name: Spiropitan (JP)) is a typical antipsychotic and research chemical belonging to the butyrophenone chemical class.^[1] It is licensed for clinical use in Japan as a treatment for schizophrenia.^[2] Additionally, spiperone was identified by compound screening to be an activator of Ca²⁺ activated Cl⁻ channels (CaCCs), thus a potential target for therapy of cystic fibrosis.^[3]

Receptor	K_i (nM)^[4]	Notes
5-HT_1A	17.3
5-HT_1B	995
5-HT_1D	2397
5-HT_1E	5051
5-HT_1F	3.98
5-HT_2A	1.17
5-HT_2B	0.8–1114.2	0.8 is bovine^[5]
5-HT_2C	922.9
5-HT₃	>10000	No data available from cloned human receptors. Data comes from rat cortex receptors and other sources.
5-HT_5A	2512	Cloned mouse receptor.
5-HT₆	1590	Cloned rat receptor.
5-HT₇	109.8
α_1A	20.4
α_1B	3.09
α_1D	8.32
D₁	398.5
D₂	0.16
D₃	0.34
D₄	1.39
D₅	4500
H₁	272
σ	353

N-Methylspiperone (NMSP) is a derivate of spiperone that is used to study the dopamine and serotonin neurotransmitter system. Labeled with the radioisotope carbon-11, it can be used for positron emission tomography.^[6]

References

^ Zheng LT, Hwang J, Ock J, Lee MG, Lee WH, Suk K (December 2008). "The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production". Journal of Neurochemistry. 107 (5): 1225–1235. doi:10.1111/j.1471-4159.2008.05675.x. PMID 18786164.
^ "Mirtazapine". Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 12 September 2011. Retrieved 4 November 2013.
^ Liang L, MacDonald K, Schwiebert EM, Zeitlin PL, Guggino WB (January 2009). "Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway". American Journal of Physiology. Cell Physiology. 296 (1): C131–C141. doi:10.1152/ajpcell.00346.2008. PMC 4116347. PMID 18987251.
^ 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 4 November 2013.
^ Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD (August 2023). "2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery". J Med Chem. 66 (16): 11027–11039. doi:10.1021/acs.jmedchem.3c01178. PMC 11073569. PMID 37584406.
^ Andrée B, Nyberg S, Ito H, Ginovart N, Brunner F, Jaquet F, et al. (August 1998). "Positron emission tomographic analysis of dose-dependent MDL 100,907 binding to 5-hydroxytryptamine-2A receptors in the human brain". Journal of Clinical Psychopharmacology. 18 (4): 317–323. doi:10.1097/00004714-199808000-00012. PMID 9690698.

[pmid18786164-1] Zheng LT, Hwang J, Ock J, Lee MG, Lee WH, Suk K (December 2008). "The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production". Journal of Neurochemistry. 107 (5): 1225–1235. doi:10.1111/j.1471-4159.2008.05675.x. PMID 18786164.

[MD-2] "Mirtazapine". Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 12 September 2011. Retrieved 4 November 2013.

[pmid18987251-3] Liang L, MacDonald K, Schwiebert EM, Zeitlin PL, Guggino WB (January 2009). "Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway". American Journal of Physiology. Cell Physiology. 296 (1): C131–C141. doi:10.1152/ajpcell.00346.2008. PMC 4116347. PMID 18987251.

[4] 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 4 November 2013.

[BenderParrLivingston2023-5] Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD (August 2023). "2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery". J Med Chem. 66 (16): 11027–11039. doi:10.1021/acs.jmedchem.3c01178. PMC 11073569. PMID 37584406.

[6] Andrée B, Nyberg S, Ito H, Ginovart N, Brunner F, Jaquet F, et al. (August 1998). "Positron emission tomographic analysis of dose-dependent MDL 100,907 binding to 5-hydroxytryptamine-2A receptors in the human brain". Journal of Clinical Psychopharmacology. 18 (4): 317–323. doi:10.1097/00004714-199808000-00012. PMID 9690698.

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v t e Antipsychotics (N05A)
Typical	Butyrophenones: Benperidol Bromperidol Bromperidol decanoate Droperidol Haloperidol^# Haloperidol decanoate Moperone Pipamperone Spiperone Timiperone Trifluperidol Diphenylbutylpiperidines: Fluspirilene Penfluridol Pimozide Phenothiazines: Acepromazine Acetophenazine Butaperazine Carphenazine (carfenazine)^‡ Chlorpromazine Cyamemazine Dixyrazine Fluphenazine Fluphenazine decanoate Fluphenazine enanthate Levomepromazine (methotrimeprazine) Mesoridazine Perazine Periciazine Perphenazine BL-1020 Perphenazine decanoate Perphenazine enanthate Piperacetazine Pipotiazine Pipotiazine palmitate Pipotiazine undecylenate Prochlorperazine Promazine Sulforidazine Thiopropazate Thioproperazine Thioridazine Trifluoperazine Triflupromazine Thioxanthenes: Chlorprothixene Clopenthixol Clopenthixol decanoate Flupentixol Flupentixol decanoate Tiotixene (thiothixene) Zuclopenthixol Zuclopenthixol acetate Zuclopenthixol decanoate
Disputed	Benzamides: Amisulpride Levosulpiride Nemonapride Remoxipride^‡ Sulpiride Sultopride Tiapride Veralipride^‡ Butyrophenones: Melperone Tricyclics: Carpipramine Clocapramine Clorotepine Clotiapine Loxapine Mosapramine Oxyprothepin decanoate Others: Molindone
Atypical	Benzisoxazole/benzisothiazoles: Iloperidone Lurasidone Paliperidone Paliperidone palmitate Perospirone Risperidone^# Ziprasidone Butyrophenones: Lumateperone Phenylpiperazines/quinolinones: Aripiprazole Aripiprazole lauroxil Brilaroxazine^† Brexpiprazole Cariprazine Tricyclics: Asenapine Clozapine^# Olanzapine (+samidorphan) Quetiapine Zotepine Others: Blonanserin Pimavanserin Sertindole
Others	Monoamine-depleting agents: Oxypertine Reserpine Tetrabenazine Others/unknown: Azacyclonol Xanomeline/trospium chloride
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III