Diphenhydramine HCl

Diphenhydramine, an antihistamine, was tested for toxicity to zebrafish embryos and larvae. Phenotypic, biochemical, behavioral, and in silico analyses were used to gain further insight into the mode of action of Diphenhydramine in a non-mammalian system. Exposure to Diphenhydramine at concentrations of 0.001-10 mg per liter did not affect survival, hatching, or malformation rate, but resulted in a significant decrease in heartbeat at 10 mg per liter after 48 h.
Hypoactivity and erratic swimming were observed at ≥1 mg per liter in the behavior assay, which may be indicative of neurotoxicity. Diphenhydramine also affected the biochemical endpoints, resulting in shifts in energy reserves, increases in cholinesterase and glutathione S-transferase activity, and a decrease in total glutathione content at 10 mg per liter. These effects may be a consequence of altered neurotransmission and oxidative stress. DNA damage occurred at ≥0.01 mg per liter and was completely repaired after 72 h in clean water. The in-silico analyses also showed high target conservation between human and zebrafish, as well as conservation of binding residues and similar docking affinities.

Fig. 1 Toxicity assessment of Diphenhydramine. (Barreto A.; et al. 2022)

Chitosan-coated alginate (CCA) nanoparticles were engineered to enhance the topical delivery of Diphenhydramine hydrochloride while minimizing systemic sedation. Using a factorial design, the alginate concentration, drug:polymer ratio and CaCl2 volume were optimized for entrapment efficiency. The selected formula showed no irritation on rat skin histopathology. Intradermal histamine challenge demonstrated significantly smaller wheal diameter versus marketed Diphenhydramine hydrochloride cream, confirming superior topical antihistaminic efficacy.

Fig. 2 Melamine-formaldehyde resin for synthesizing highly porous carbon materials. (Aziz S N.; et al. 2023)