Chemical Properties
Off-White Solid
Uses
Neuroleptic agent related structurally to thiothixene. Antipsychotic; neuroleptic agent; dopamine receptor antagonist
Definition
ChEBI: Cis-flupenthixol dihydrochloride is the dihydrochloride salt of cis-flupenthixol. It has a role as a geroprotector. It contains a cis-flupenthixol(2+).
General Description
cis-(Z)-Flupenthixol dihydrochloride?(FLU) is a thioxanthene drug. DRD1 (dopamine receptor D1) codes for D1Rs and is located on human chromosome 5q35.2. Dopamine D1 is expressed on lung alveolar type I cells.
Biological Activity
ki: 0.38 nm for dopamine d2 receptorscis-flupenthixol is an antagonist at dopamine d2 receptors.dopamine receptor d2 is encoded by the drd2 gene. it has been suggested that dopamine receptors are the action site of antipsychotic drugs. the dopamine d2 receptor is also the main receptor for all antipsychotic drugs.
Biochem/physiol Actions
Antipsychotic; neuroleptic agent; dopamine receptor antagonist. cis-(Z)-Flupenthixol dihydrochloride?(FLU) is used to treat schizophrenia and anxiolytic and depressive disorders Dopamine D1?plays a major role in lung fluid homeostasis. It controls the airway smooth muscle tone by producing adenylyl cyclase/cAMP, that would favor airway relaxation in asthmatics. Dopamine in the lung, serves as a neurotransmitter and noradrenaline precursor.
in vitro
the effects of striatal kainic acid lesions on [3h] cis-flupenthixol and [3h]spiperone binding to dopamine receptors were examined in a previous study. significant reductions in both binding parameters were observed, and [3h] cis-flupenthixol binding was depleted to a greater level than [3h]spiperone binding. reductions in both binding were correlated with reductions in glutamic acid decarboxylase activity [1].
in vivo
in a previous animal study rats were conditioned to associate an environment with immediate or delayed effects of pre-treatment with either cis-flupenthixol or saline vehicle. results showed that vehicle-treated control animals developed the normal pattern of cpps and cis-flupenthixol-caused da receptor antagonism could prevent the expression of cocaine cpps but it did not alter the expression of cocaine-induced cpas [2].
References
[1] cross aj, waddington jl. kainic acid lesions dissociate [3h] spiperone and [3h]cis-flupenthixol binding sites in rat striatum. eur j pharmacol. 1981 may 8;71(2-3):327-32.
[2] wenzel jm, su zi, shelton k, dominguez hm, von furstenberg va, ettenberg a. the dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats. pharmacol biochem behav. 2013 dec;114-115:90-6.
[3] cookson ib. the effects of a 50% reduction of cis(z)-flupenthixol decanoate in chronic schizophrenic patients maintained on a high dose regime. int clin psychopharmacol. 1987 apr;2(2):141-9.
