Chlorprothixene (hydrochloride) is an antagonist of dopamine receptor and histamine receptors [1]. Chlorprothixene is also an inhibitor of GABAA receptor [2]. All of these three receptors are implicated in many neurological processes, including motivation, pleasure, cognition, memory and learning.

In vitro: Chlorprothixene exihibited strong binding affinities to dopamine and histamine receptors, The Ki values of D1, D2, D3, D5 and H1 were 18nM, 2.96 nM, 4.56 nM, 9 nM and 3.75 nM, respectively. Chlorprothixene showed little affinity to H3 with the Ki value of >1000 nM[1]. In COS-7 cells transiently expressed rat 5-HT7 receptors and HEK-293 cells stably transfected with rat 5-HT6, the Ki values of chlorprothixene were 5.6 nM and 3 nM, respectively [3]. In Vero 76 cells, chlorprothixene treatment inhibited SARS-CoV replication, with IC50 of 16.7 μM for Urbani strain, 13.0 μM for Frankfurt-1, 18.5 μM for CHUK-W1 and 15.8 μM for Toronto-2 [4].

In vivo: In rat brain depressing the release of hypothalamic and hypophyseal hormones, chlorprothixene blocked postsynaptic mesolimbic dopaminergic D1 and D2 receptors [5]. Chlorprothixene treatment restored normal ceramide concentrations in murine bronchial epithelial cells, reduced inflammation in the lungs of mice with cystic fibrosis (CF) and prevented infection with Pseudomonas aeruginosa [6].

References:
[1] Von Coburg Y, Kottke T, Weizel L, et al.  Potential utility of histamine H 3 receptor antagonist pharmacophore in antipsychotics[J]. Bioorganic & medicinal chemistry letters, 2009, 19(2): 538-542.
[2] Squires R F, Saederup E.  Clozapine and several other antipsychotic/antidepressant drugs preferentially block the same ‘core’fraction of GABA A receptors[J]. Neurochemical research, 1998, 23(10): 1283-1290.
[3] Roth B L, Craigo S C, Choudhary M S, et al.  Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors[J]. Journal of Pharmacology and Experimental Therapeutics, 1994, 268(3): 1403-1410.
[4] Barnard D L, Day C W, Bailey K, et al.  Is the anti-psychotic, 10-(3-(dimethylamino) propyl) phenothiazine (promazine), a potential drug with which to treat SARS infections: Lack of efficacy of promazine on SARS-CoV replication in a mouse model[J]. Antiviral research, 2008, 79(2): 105-113.
[5] Gey K F, Pletscher A.  Influence of chlorpromazine and chlorprothixene on the cerebral metabolism of 5-hydroxytryptamine, norepinephrine and dopamine[J]. Journal of Pharmacology and Experimental Therapeutics, 1961, 133(1): 18-24.
[6] Becker K A, Riethmuller J, Luth A, et al.  Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis[J]. American journal of respiratory cell and molecular biology, 2010, 42(6): 716-724.]