Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performance

Br J Pharmacol. 2009 May;157(1):76-85. doi: 10.1111/j.1476-5381.2008.00103.x. Epub 2009 Feb 13.


Background and purpose: Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia.

Experimental approach: Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials.

Key results: Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times.

Conclusions and implications: The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chlorpheniramine / adverse effects
  • Choice Behavior / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials
  • Female
  • Histamine H1 Antagonists / adverse effects*
  • Humans
  • Lorazepam / adverse effects
  • Male
  • Photic Stimulation
  • Psychomotor Performance / drug effects*
  • Reaction Time / drug effects
  • Young Adult


  • Histamine H1 Antagonists
  • dexchlorpheniramine
  • Chlorpheniramine
  • Lorazepam