8-hydroxyloxapine

8-hydroxy Loxapine (8-OH loxapine) is a metabolite formed when loxapine , an atypical antipsychotic, is metabolized by the cytochrome P450 isoform CYP1A2. Loxapine displays high affinity for histamine, serotonin (5-HT), dopamine, and α₁-adrenergic receptors (K_i values = 7, 7.7, 9.5, 12, and 31 nM for H₁, 5-HT_2A, 5-HT_2C, D₂, and α_1A-adrenergic receptors, respectively). It reduces agitation associated with schizophrenia or bipolar disorder. 8-OH Loxapine is considered inactive as it has relatively low affinity to dopamine and 5-HT receptors compared to the parent compound, however, 8-OH loxapine inhibits [¹⁴C]5-HT uptake in vitro (IC₅₀ = 2 μM in human platelets).

Pale Yellow Solid

The inactive

[1] MD P S, PH.D  Hubert H M V T Ph D  Roy Corbett Ph D. Atypical Neuroleptics Have Low Affinity for Dopamine D2 Receptors or Are Selective for D4 Receptors[J]. Neuropsychopharmacology, 1997, 16 2: 93-110. DOI: 10.1016/s0893-133x(96)00187-x
[2] YIN CHEONG WONG  Zhong Z  Siu Kwan Wo. Investigation of the disposition of loxapine, amoxapine and their hydroxylated metabolites in different brain regions, CSF and plasma of rat by LC–MS/MS[J]. Journal of pharmaceutical and biomedical analysis, 2012, 58: Pages 83-93. DOI: 10.1016/j.jpba.2011.09.020
[3] ANDREW J GOUDIE. H1-histamine Receptor Affinity Predicts Short-term Weight Gain for Typical and Atypical Antipsychotic Drugs[J]. Neuropsychopharmacology, 2003, 28 12: 2209-2209. DOI: 10.1038/sj.npp.1300291
[4] JUSTIN FADEN L C. Examining the safety, efficacy, and patient acceptability of inhaled loxapine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults[J]. Neuropsychiatric Disease and Treatment, 2019, 15 1: 2273-2283. DOI: 10.2147/ndt.s173567
[5] A. FULTON  G. D B  T Norman. Ligand binding and platelet uptake studies of loxapine, amoxapine and their 8-hydroxylated derivatives[J]. Journal of affective disorders, 1982, 4 2: Pages 113-119. DOI: 10.1016/0165-0327(82)90041-6