Low dosage promethazine and loratadine negatively affect neuromotor function

Clin Neurophysiol. 2012 Apr;123(4):780-6. doi: 10.1016/j.clinph.2011.07.046. Epub 2011 Aug 30.


Objectives: Determine how the sedating antihistamine promethazine and non-sedating antihistamine loratadine at a dose of 10mg influence voluntary and involuntary motor processes in the hours following ingestion and the morning after ingestion.

Methods: Eight healthy young adults were recruited into a human double-blind, placebo-controlled, three-way crossover study. Neuromotor function was examined using a battery of controlled reaction time, postural tremor, and heart rate variability measures. Neuromotor function was assessed 4 times for each of the promethazine, loratadine and placebo interventions; pre-ingestion, 1h post-ingestion, 2h post-ingestion, and the following day.

Results: Self-perceived levels of drowsiness increased only after ingestion of promethazine. However, both antihistamines had negative effects on simple reaction time, choice reaction time, the RMS and peak power amplitude of postural tremor, and autonomic cardiac regulation.

Conclusions: The presence of selective neuromotor deficits following ingestion of promethazine and loratadine suggest that sedating and non-sedating antihistamines alter neuromotor function. It is possible that the H(1) antagonists used in this study have antimuscarinic effects, which may impact on the central dopaminergic system that plays a role in modulating several CNS processes associated with movement.

Significance: Antihistamines are one of the most commonly procured over-the-counter medications. The current study suggests that taking non-sedating antihistamines to avoid the adverse drug reaction of drowsiness may not avoid unwanted motor control side-effects.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Histamine H1 Antagonists / administration & dosage*
  • Histamine H1 Antagonists / pharmacology*
  • Histamine H1 Antagonists, Non-Sedating / administration & dosage*
  • Histamine H1 Antagonists, Non-Sedating / pharmacology*
  • Humans
  • Loratadine / administration & dosage*
  • Loratadine / pharmacology*
  • Male
  • Motor Neurons / drug effects*
  • Movement / drug effects*
  • Promethazine / administration & dosage*
  • Promethazine / pharmacology*
  • Reaction Time / drug effects
  • Sleep Stages / drug effects
  • Tremor / chemically induced
  • Young Adult


  • Histamine H1 Antagonists
  • Histamine H1 Antagonists, Non-Sedating
  • Loratadine
  • Promethazine