Dimenhydrinate exhibits a diverse range of bioactivities across multiple biochemical assays and targets. It demonstrates significant potency in inducing erasure of genomic imprints, inhibiting Aldehyde Dehydrogenase 1 (ALDH1A1), and Hydroxyacyl-Coenzyme A Dehydrogenase, Type II (HADH2). Additionally, it is a substrate of Cytochrome P450 2D6 and shows bioactivity in Cytochrome panel assays. The compound acts as an agonist for androgen receptor signaling and the antioxidant response element (ARE) signaling pathway. Moreover, it inhibits the human hERG channel activity and the ROR-gamma signaling pathway.
Dimenhydrinate has activity against various adrenergic receptors, the norepinephrine transporter, calcium channel Type L, and dopamine transporter. It also shows notable activity in histamine H1 receptor, serotonin receptor subtypes (5-HT2A, 5-HT2B, and 5-HT2C), and Sigma1 receptor binding assays, indicating broad pharmacological effects. It further inhibits sodium fluorescein uptake in OATP1B3 and OATP1B1-transfected CHO cells.
Evaluation in DrugMatrix assays illustrates alterations in several physiological parameters like liver enzymes, kidney function markers, electrolytes, lipid profiles, hematological parameters, and immune cell counts, suggesting potential effects on liver and kidney function, blood composition, and immune response.
For biliary transport, Dimenhydrinate shows weak or no inhibitory effect on human BSEP, MRP2, MRP3, and MRP4 activities, with IC50 values substantially higher than effective concentrations. It induces no drug-induced liver injury.
In antiviral studies, Dimenhydrinate shows moderate to weak inhibition of SARS-CoV-2 cytotoxicity and 3CL-Pro protease activity, identifiable by varying inhibition values across different assays at tested concentrations.
The compound has also shown selective inhibition of the HDAC6 enzyme, suggesting potential as an HDAC6 inhibitor based on assays utilizing different peptide substrates..
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