SPIPERONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H26FN3O2
Molecular Weight	395.4698
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(C=C1)C(=O)CCCN2CCC3(CC2)N(CNC3=O)C4=CC=CC=C4

InChI

InChIKey=DKGZKTPJOSAWFA-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323626558
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18786164 | https://www.ncbi.nlm.nih.gov/pubmed/10202608 | https://www.ncbi.nlm.nih.gov/pubmed/8866760

Spiperone (Spiroperidol; brand name: Spiropitan (JP)) is a typical antipsychotic and research chemical belonging to the butyrophenone chemical class. Spiperone is selective D2 dopamine receptor antagonist; α1B-adrenoceptor antagonist; mixed 5-HT2A/5-HT1 serotonin receptor antagonist. 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. Spiperone is widely used as a pharmacological tool for studying neurotransmitter receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26227779	Antagonist 2778	1.08 nM [Ki]
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23403082	Antagonist 2778	0.2 nM [Ki]
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26227779	Antagonist 2778	0.48 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10202608	Diagnostic		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The effect of 5-hydroxytrytamine synthesis inhibitors on neuroleptic-induced catalepsy in rats.	1975	1172422
Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy.	1975 Jan-Feb	1168927
Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.	2001	11341484
Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer.	2001	11250742
Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.	2001	11226678
Modulation of 5-HT(1A) receptor activation by its interaction with wild-type and mutant g(alphai3) proteins.	2001	11077069
Alteration of dopamine transport in the striatum and nucleus accumbens of ovariectomized and estrogen-primed rats following N-(p-isothiocyanatophenethyl) spiperone (NIPS) treatment.	2001 Apr	11403989
The role of D2-like dopamine receptors in the locomotor stimulant effects of cocaine in mice.	2001 Apr	11374338
Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling.	2001 Apr	11259531
Effects of dopaminergic agents on carrageenan hyperalgesia after intrathecal administration to rats.	2001 Apr 20	11334867
D(3) dopamine receptors in rat spinal cord: implications for sensory and motor function.	2001 Apr 27	11297811
Cis- and trans-N-benzyl-octahydrobenzo[g]quinolines. Adrenergic and dopaminergic activity studies.	2001 Apr 9	11294383
Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype.	2001 Aug 3	11369753
Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study.	2001 Feb	11199948
Differential modulation by GTPgammaS of agonist and inverse agonist binding to h5-HT(1A) receptors revealed by [3H]-WAY100,635.	2001 Jan	11159702
The effect of nicotine and haloperidol co-treatment on nicotinic receptor levels in the rat brain.	2001 Jan 31	11165378
Affinity of serotonin receptor antagonists and agonists to recombinant and native alpha1-adrenoceptor subtypes.	2001 Jun	11459121
Stimulation of sodium-dependent inorganic phosphate transport by activation of Gi/o-protein-coupled receptors by epinephrine in MC3T3-E1 osteoblast-like cells.	2001 Jun	11425646
The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution.	2001 Jun	11414657
Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice.	2001 Jun	11378281
Effects of intrastriatal infusion of D2 and D3 dopamine receptor preferring antagonists on dopamine release in rat dorsal striatum (in vivo microdialysis study).	2001 Mar	11401421
Failure of AH11110A to functionally discriminate between alpha(1)-adrenoceptor subtypes A, B and D or between alpha(1)- and alpha(2)-adrenoceptors.	2001 Mar	11275009
S 14506: novel receptor coupling at 5-HT(1A) receptors.	2001 Mar	11166326
Dopamine depletion with 6-OHDA enhances dopamine D1-receptor modulation of potassium currents in retinal bipolar cells.	2001 Mar-Apr	11417806
D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: influence of withdrawal period.	2001 May	11252025
Differential effects of 5-HT1A receptor deletion upon basal and fluoxetine-evoked 5-HT concentrations as revealed by in vivo microdialysis.	2001 May 25	11376590
Effects of endogenous neurotransmitters on the in vivo binding of dopamine and 5-HT radiotracers in mice.	2001 Nov	11682251
Expression of catecholaminergic mRNAs in the hyperactive mouse mutant coloboma.	2001 Nov 30	11731016
Dopamine inhibits vasopressin action in the rat inner medullary collecting duct via alpha(2)-adrenoceptors.	2001 Sep	11504796
Dosing time-dependent tolerance of catalepsy by repetitive administration of haloperidol in mice.	2001 Sep	11504791
Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179).	2001 Sep 17	11549463
New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities.	2001 Sep 3	11527728
Occurrence of dopaminergic (D(2)) receptors within the rabbit pulmonary circulation.	2002	12220945
Atmospheric pressure laser desorption/chemical ionization mass spectrometry: a new ionization method based on existing themes.	2002	11921247
Metachlorophenylpiperazine (m-CPP) induced intracavernous pressure responses in anaesthetized rats.	2002 Aug	12152119
Functional cooperation between neurosteroids and D2 dopamine antagonists on KCl-evoked [3H]noradrenaline release: modulation by calcium channel blockers.	2002 Dec	12472876
Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors.	2002 Feb-Nov	12503636
Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.	2002 Jul	12065741
Functional screening of G protein-coupled receptors by measuring intracellular calcium with a fluorescence microplate reader.	2002 Jun	12097186
Adenosinergic modulation of the discriminative-stimulus effects of methamphetamine in rats.	2002 Jun	12073161
The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype.	2002 Mar	11906967
Enhanced detection of receptor constitutive activity in the presence of regulators of G protein signaling: applications to the detection and analysis of inverse agonists and low-efficacy partial agonists.	2002 May	11961140
The effects of dopamine synthesis inhibitors and dopamine antagonists on regeneration in the hydra Hydra attenuata.	2002 May-Jun	12135343
Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures.	2002 Nov	12453049
Spreading depression: imaging and blockade in the rat neocortical brain slice.	2002 Nov	12424306
Serotonin-induced MMP-13 production is mediated via phospholipase C, protein kinase C, and ERK1/2 in rat uterine smooth muscle cells.	2002 Nov 8	12213812
Antibody capture assay reveals bell-shaped concentration-response isotherms for h5-HT(1A) receptor-mediated Galpha(i3) activation: conformational selection by high-efficacy agonists, and relationship to trafficking of receptor signaling.	2002 Sep	12181435
Corticotropin-releasing factor as well as opioid and dopamine are involved in tail-pinch-induced food intake of rats.	2003	12559107
In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: differential findings with [3H]raclopride versus [3H]spiperone.	2003 Feb	12527818
Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter.	2003 Jan	12522083

Patents

Sample Use Guides

In Vivo Use Guide

Rat: i.v. injection 12 mkCi (180 ng).

Route of Administration: Intravenous

In Vitro Use Guide

Aliquots of lymphocyte suspension containing 1 x 106- 2 x 106 cells in a final volume of 1.0 mL were incubated in duplicate for 1 hour at 37°C with varying concentrations of 3H-spiperone (0.1—4 nM) in the presence or absence of 10 5 M haloperidol. Cell viability, checked in a number of samples incubated in the absence of 3H-spiperone by their ability to exclude trypan blue, always exceeded 98%. After incubation, the samples were filtered (type GF/B) and rinsed six times with 4 ml cooled buffer B. The filters were dried and transferred to mini-vials with 5 mL hydro-luma scintillation fluid; radioactivity was counted in a liquid scintillation counter.

Name

Type

Language

SPIPERONE

Official Name

English

spiperone [INN]

Common Name

English

NSC-170983

Code

English

R-5147

Code

English

SPIPERONE [MART.]

Common Name

English

SPIROPITAN

Brand Name

English

Spiperone [WHO-DD]

Common Name

English

SPIPERONE [MI]

Common Name

English

SPIPERONE [USAN]

Common Name

English

SPIPERONE [JAN]

Common Name

English

R 5147

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C28197