Spiperone HCl

Spiperone hydrochloride (Spiroperidol hydrochloride) is a selective dopamine D2 receptor (Ki values of 0.06 nM, 0.6 nM, 0.08 nM, ~350 nM, ~3500 nM for D2, D3, D4, D1 and D5 receptors, respectively) and 5-HT2A/5-HT1A receptor (Kis of 1 nM/49 nM) antagonist. Spiperone hydrochloride is also a selective α1B-adrenoceptor antagonist. Spiperone hydrochloride activates calcium-activated chloride channel (CaCC). Antipsychotic and anti-inflammatory activities[1][2][3][4][5].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Chloride Channel

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

D2 Receptor:0.06 nM (Ki)

D1 Receptor:~350 nM (Ki)

D3 Receptor:0.6 nM (Ki)

D4 Receptor:0.08 nM (Ki)

D5 Receptor:~3500 nM (Ki)

5-HT2A Receptor:1 nM (Ki)

5-HT1A Receptor:49 nM (Ki)

α1B-adrenoceptor

Calcium-activated chloride channel

Spiperone is a potent intracellular Ca2+ enhancer (EC50=9.3 μM) and stimulates intracellular Ca2+ through a protein tyrosine kinase-coupled phospholipase C-dependent pathway, which results in increased secretion of Cl- in Calu-3 and CFBE41o- cell monolayers[2]. Spiperone significantly decreases the production of nitric oxide in lipopolysaccharide-stimulated BV-2 microglia cells, primary microglia and primary astrocyte cultures. Spiperone also significantly inhibits nitric oxide production in ATP-stimulated primary microglia cultures. Spiperone markedly decreases the production of TNF-α in BV-2 microglia cells. Spiperone attenuates the expression of inducible nitric oxide synthase and proinflammatory cytokines such as IL-1β and TNF-α at mRNA levels in BV-2 microglia cells[3].

Spiperone (1.5 mg/kg; intraperitoneal injection; on days 1, 3, 6, 7, and 13-21; C57Bl/6 mice) treatment reduces infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevents the growth of the connective tissue in the parenchyma of Bleomycin lungs[6]. Animal Model: C57Bl/6 mice (7-8-week-old) induced pulmonary fibrosis by Bleomycin[6] Dosage: 1.5 mg/kg Administration: Intraperitoneal injection; on days 1, 3, 6, 7, and 13-21 Result: Reduced infiltration of the alveolar interstitium and alveolar ducts with inflammatory cells and prevented the growth of the connective tissue in the parenchyma of bleomycin lungs.

[1]. P Seeman, et al. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):264-70.

[2]. Lihua Liang, et al. Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway. Am J Physiol Cell Physiol. 2009 Jan;296(1):C131-41.

[3]. Long Tai Zheng, et al. The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production. J Neurochem. 2008 Dec;107(5):1225-35.

[4]. Richard A Glennon, et al. Ketanserin and spiperone as templates for novel serotonin 5-HT(2A) antagonists. Curr Top Med Chem. 2002 Jun;2(6):539-58.

[5]. Andrea E Errasti, et al. Human umbilical vein vasoconstriction induced by epinephrine acting on alpha1B-adrenoceptor subtype. Am J Obstet Gynecol. 2003 Nov;189(5):1472-80.

[6]. E G Skurikhin, et al. Effect of spiperone on mesenchymal multipotent stromal and hemopoietic stem cells under conditions of pulmonary fibrosis. Bull Exp Biol Med. 2014 May;157(1):132-7.