Diphenhydramine is widely used as an over-the-counter antihistamine. However, the specific human cytochrome P450 (P450) isozymes that mediate the metabolism of diphenhydramine in the range of clinically relevant concentrations (0.14-0.77 microM) remain unclear. Therefore, P450 isozymes involved in N-demethylation, a main metabolic pathway of diphenhydramine, were identified by a liquid chromato...

Substrate specificity and pH dependence of the transport system for diphenhydramine were investigated in Caco-2 cell monolayers. Diphenhydramine uptake was not affected by any typical substrate for the renal organic cation transport system except procainamide. Along with procainamide, tertiary amine compounds with N-dimethyl or N-diethyl moieties in their structures inhibited the diphenhydramin...

Effects of histamine H1-receptor antagonists on L-dopa-induced behavioral excitement were examined in mice to confirm behaviorally the inhibition of dopamine uptake by these compounds. L-Dopa (100-300 mg/kg, s.c.) combined with pargyline hydrochloride (80 mg/kg, i.p.) caused a dose-dependent behavioral excitement. The marked excitement induced by L-dopa (300 mg/kg) plus pargyline was significan...

The pain caused by cancer treatment-related oral mucositis is often described as the most excruciating symptom (1). Frequently, it leads to reduced ingestion, malnutrition, and sometimes postponement or withdrawal of the therapy (1). For health care providers, adequate pain treatment is a major challenge. Treatments that have varying degrees of success include antibiotics, antifungal, antiviral...

Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furtherm...

The aim of this study was to evaluate the vehicle effect on in vitro diffusion of Diphenhydramine hydrochloride (DPH) from new five topical formulations: microemulsion (A), microemulsion+silica (B), Na Alginate emulgel (C), Carbopol cream (D) and hydroxyethylcellulose gel (E).Furthermore, the skin irritation potential and the formulation effect on skin reaction induced by histamine were investi...

Diphenhydramine, as an antihistamine drug is widely used for the treatment of allergies. However, being classified as an over the counter medication and the general belief on the low adverse effect profile of this drug has made it widely accessible to the families. Recent reports of diphenhydramine intoxication and mortality, noticeably in children and infants have raised some serious concerns....