H1-receptor antagonists. Comparative tolerability and safety

Drug Saf. 1994 May;10(5):350-80. doi: 10.2165/00002018-199410050-00002.


First-generation histamine H1-receptor antagonists, such as diphenhydramine, triprolidine, hydroxyzine or chlorpheniramine (chlorphenamine), frequently cause somnolence or other CNS adverse effects. Second-generation H1-antagonists, such as terfenadine, astemizole, loratadine and cetirizine, represent a true advance in therapeutics. In manufacturers' recommended doses, they have a more favourable benefit/risk ratio than their predecessors with regard to lack of CNS effects, and do not exacerbate the adverse CNS effects of alcohol or other CNS-active chemicals. Rarely, some of the newer H1-antagonists may cause cardiac dysrhythmias after overdose or under other specific conditions. The concept of a risk-free H1-antagonist is proving to be an oversimplification. An H1-antagonist absolutely free from adverse effects under all circumstances is not yet available for use. The magnitude of the beneficial effects of each H1-antagonist should be related to the magnitude of the unwanted effects, especially in the CNS and cardiovascular system, and a benefit-risk ratio or therapeutic index should be developed for each medication in this class.

Publication types

  • Review

MeSH terms

  • Abnormalities, Drug-Induced
  • Animals
  • Blood-Brain Barrier / drug effects
  • Cardiovascular System / drug effects*
  • Central Nervous System / drug effects*
  • Drug Interactions
  • Electrocardiography / drug effects
  • Electroencephalography / drug effects
  • Ethanol / pharmacology
  • Histamine H1 Antagonists / adverse effects*
  • Histamine H1 Antagonists / toxicity
  • Humans
  • Pharmacoepidemiology
  • Psychomotor Performance / drug effects


  • Histamine H1 Antagonists
  • Ethanol