69-23-8 (free base)

Fluphenazine dimaleate is a potent, orally active phenothiazine-based dopamine receptor antagonist. Fluphenazine dimaleate blocks neuronal voltage-gated sodium channels. Fluphenazine dimaleate acts primarily through antagonism of postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular neural pathways. Fluphenazine dimaleate can antagonize Methylphenidate-induced stereotyped gnawing and inhibit climbing behaviour in mice. Fluphenazine dimaleate can be used for researching psychosis and painful peripheral neuropathy associated with diabetes and has potential to inhibit SARS-CoV-2[1][2][3][4][6].

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

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> SARS-CoV

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

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Dopamine receptor, Sodium channels, SARS-CoV-2[1][2]

Fluphenazine (1 mg/kg; IG, treated from day 6 to day 15 of gestation) causes malformations in pregnant mice[5]. Fluphenazine (0.125-1 mg/kg; IP, single dosage) antagonizes Methylphenidate-induced stereotyped gnawing; inhibits significantly climbing behaviour[6]. Animal Model: Mature female Swiss-Webster mice[5] Dosage: 1 mg/kg Administration: IG, treated from day 6 to day 15 of gestation Result: Significantly reduced fetal weight and length, increased the incidence of incomplete ossification of sternebrae and skull bones. Animal Model: Mice (injected with 60 mg/kg Methylphenidate)[6] Dosage: 0.125, 0.25, 0.5, and 1 mg/kg Administration: IP, single dosage Result: Antagonized Methylphenidate-induced stereotyped gnawing; inhibited significantly climbing behaviour in mice at 0.0625-0.5 mg/kg, and at the dose of 1 mg/kg abolished this effect completely.

[1]. Zhou X, et al. The neuroleptic drug, fluphenazine, blocks neuronal voltage-gated sodium channels. Brain Res. 2006 Aug 23;1106(1):72-81.

[2]. Nazeam J, et al. Based on Principles and Insights of COVID-19 Epidemiology, Genome Sequencing, and Pathogenesis: Retrospective Analysis of Sinigrin and ProlixinRX (Fluphenazine) Provides Off-Label Drug Candidates. SLAS Discov. 2020 Dec;25(10):1123-1140.

[3]. Siragusa S, Bistas KG, Saadabadi A. Fluphenazine. 2022 May 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.

[4]. Davis JL, et al. Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. JAMA. 1977 Nov 21;238(21):2291-2.

[5]. Abdel-Hamid HA, et al. Teratogenic effect of diphenylhydantoin and/or fluphenazine in mice. J Appl Toxicol. 1996 May-Jun;16(3):221-5.

[6]. Langwiński R, Niedzielski J. Narcotic analgesics and stereotyped behaviour in mice. Naunyn Schmiedebergs Arch Pharmacol. 1980 Jul;312(3):225-7.