Regarding cardiovascular effects, DMH decreased vascular reactivity to phenylephrine and acetylcholine. We observed that the combination of DPH and 8-Cl-T was identified as the responsible for increasing blood pressure and heart rate in the biological model used.

ABSTRACT

Several studies have described the sedative effects of dimenhydrinate (DMH), although others report a stimulant effect on psychomotor functions. Because the first generation of antihistamines was shown to seriously impair cognitive psychomotor and driving performance in healthy volunteers, the aim of our research was to determine the effect of DMH by testing physical activity and cognitive and cardiovascular functions using an animal model to identify a possible stimulatory effect. The study protocol consisted of two phases. The first was designed to analyze the stimulating motor effect of DMH. Four study groups were formed: (1) vehicle (Veh), (2) modafinil (MOD), (3) DMH at 50 mg/kg (DMH-50), and (4) DMH at 200 mg/kg (DMH-200). Motor coordination and balance, physical activity, hemodynamics, and nitrous oxide (NO) quantification were performed. In the second phase, we sought to discriminate the compound in DMH that generates the stimulating effect. In this case, the study groups were (1) Veh, (2) MOD, (3) DMH, (4) diphenhydramine (DPH), (5) 8-chlorotheophylline (8-Cl-T), and (6) theophylline (TEO). In this phase, we quantified glucose and insulin levels, behavior, physical activity, blood pressure, and vascular reactivity to phenylephrine and acetylcholine. Findings showed that DMH might improve a motor and physical stimulating effect but also increased NO levels in the lungs. DPH promoted a compulsive-like behavior that diminished with 8-Cl-T. Regarding cardiovascular effects, DMH decreased vascular reactivity to phenylephrine and acetylcholine. Finally, in the DMH formulation, 8-Cl-T was identified as the compound responsible for increasing blood pressure and heart rate.