Cardiac Autonomic Modulation Following a 50 mg Oral Dose of Dimenhydrinate in Healthy Young Adults: A Double-Blind Randomized Controlled Trial

Abstract

Background: Heart rate variability (HRV) reflects beat-to-beat changes in the cardiac cycle that result from interactions between sinus node cells and the autonomic nervous system. Dimenhydrinate is a first-generation H1 receptor antihistamine of the monoethanolamine class. Objectives: This study aimed to evaluate the effects of oral dimenhydrinate on cardiac autonomic activity using heart rate variability (HRV) indices. Methods: This double-blind crossover study included volunteers who attended two sessions separated by a 2-week interval. In each session, a 5-minute electrocardiogram (ECG; lead II) was recorded at baseline and at multiple time points within 4 hours after oral administration of either placebo or 50 mg dimenhydrinate. Time- and frequency-domain HRV parameters were calculated and statistically analyzed. Results: Placebo had no significant effects on any HRV indices. Administration of 50 mg dimenhydrinate resulted in a significant increase in mean SDNN (standard deviation of normal-to-normal intervals) at 90 minutes. At 4 hours after administration, both RMSSD (root mean square of successive differences) and PNN50% (percentage of successive NN intervals differing by more than 50 ms) were significantly elevated in the dimenhydrinate group, indicating enhanced parasympathetic modulation. Conclusions: These findings suggest that oral dimenhydrinate, which crosses the blood-brain barrier, modulates cardiac autonomic balance by enhancing parasympathetic activity and reducing sympathetic dominance via H1 receptor antagonism.