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Performance effects of antihistamines.

In 1988 an estimated 30 million Americans spent more than $500 million for single-entity antihistamines. Classic first-generation antihistamines, which are available without prescription, can cross the blood-brain barrier and have been reported to produce various central nervous system effects. Sedation, the most common adverse effect of these agents, occurs in 10% to 25% of antihistamine users. Drowsiness has been attributed to the blockade of central histaminergic receptors; antagonism of other brain receptors, such as serotonergic, cholinergic, and central alpha-adrenergic receptors, has also been proposed. The newer second-generation H1-receptor antagonists are typically large, lipophobic molecules with a charged side chain and are extensively bound to albumin. Consequently, these agents have difficulty entering the brain, and they appear no more likely to induce sedation than does placebo. The effects of antihistamines on psychomotor reflexes and driving, antihistamine-induced drowsiness, and interaction of antihistamines with alcohol and tranquilizers have been studied with numerous methodologies. The centrally acting first-generation agents commonly cause greater performance decrements as compared with the newer, nonsedating, second-generation antihistamines.

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