EC50: 1.24 μM

Fluphenazine is a dopamine D1 and D2 receptor inhibitor.

Dopamine D1 and D2 receptor immunohistochemistry has been used to study the structure of the adult rat arcuate-median eminence complex, particularly in relation to the tubero-infundibular dopamine neurons.

In vitro: Previous study showed that both phenothiazines of fluphenazine and perphenazine induced concentration-dependent loss in cell viability with EC50s to be 1.24 and 2.76 μM for fluphenazine and perphenazine, respectively. Moreover, fluphenazine at 1.0 μM and perphenazine at 1.0 and 3.0 μM could inhibit melanogenesis and decrease the content of microphthalmia-associated transcription factor. In addition, both fluphenazine and perphenazine at higher concentrations caused depletion of melanocytes antioxidant status, indicating oxidative stress induction [1].

In vivo: Systemic fluphenazine could effectively attenuate mechanical allodynia in rat neuropathic pain models at 0.03-0.3 mg/kg doses, which approximated those used in rodent models of psychosis. For antiallodynic effect, fluphenazine was able to effectively suppress the ectopic discharges in injured afferent fibers without affecting the propagation of action potentials in an ex-vivo DRG-nerve preparation from CCI rats [2].

Clinical trial: Fluphenazine, which is sold under the brand names Prolixin, is clinically used as an antipsychotic medication in the treatment of chronic psychoses such as schizophrenia. In addition, fluphenazine is about equal in effectiveness to low-potency antipsychotics (https://en.wikipedia.org/wiki/Fluphenazine).

References:
[1] Otreba M et al.  Fluphenazine and perphenazine impact on melanogenesis and antioxidant enzymes activity in normal human melanocytes. Acta Poloniae Pharmaceutica-Drug Research, July-August 2016, 73(4):903-911.
[2] Dong XW,Jia Y,Lu SX,Zhou X,Cohen-Williams M,Hodgson R,Li H,Priestley T.  The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology (Berl). 2008 Jan;195(4):559-68.