Hydroxyzine is a prescription medication often used to manage a range of conditions, including anxiety, tension, and various allergic reactions. It also provides relief for itching (pruritus) or hives. Additionally, it can be administered for sedation before medical procedures.
Primary Action as an H1 Receptor Antagonist
Hydroxyzine is an antagonist of the histamine H1 receptor. Histamine is a natural body chemical involved in wakefulness and allergic responses. When allergens are encountered, mast cells and basophils release histamine, which binds to H1 receptors and causes symptoms like itching, hives, and swelling.
Hydroxyzine blocks histamine from binding to these H1 receptors. Imagine histamine as a key and the H1 receptor as a lock. Hydroxyzine acts as an object that prevents the histamine key from entering. This action reduces the effects typically triggered by histamine, alleviating allergic symptoms.
Central Nervous System Sedative and Anxiolytic Effects
Hydroxyzine crosses the blood-brain barrier, classifying it as a first-generation antihistamine. In the brain, histamine is a neurotransmitter that maintains wakefulness. When hydroxyzine blocks H1 receptors in the central nervous system, it interrupts wakefulness signals.
This interruption calms the brain, causing sedation and drowsiness. Reduced central nervous system activity contributes to its anxiolytic properties, alleviating tension and anxiety. Its sedative properties occur at a subcortical level in the brain.
Interaction with Other Neurotransmitter Systems
Hydroxyzine also interacts with other neurotransmitter systems, contributing to its effects and side-effect profile. It acts as an antagonist at serotonin 5-HT2A receptors, which contributes to its anti-anxiety properties and distinguishes it from some other antihistamines.
Hydroxyzine also exhibits antagonist effects on muscarinic acetylcholine receptors, although its affinity for these receptors is lower compared to some other first-generation antihistamines. This anticholinergic action can lead to common side effects such as dry mouth, blurred vision, and urinary retention. Furthermore, hydroxyzine shows a weaker antagonism at dopamine D2 receptors, which further shapes its pharmacological profile.
The Role of the Active Metabolite Cetirizine
The liver metabolizes hydroxyzine into its active metabolite, cetirizine. Cetirizine is the active ingredient in common over-the-counter allergy medications like Zyrtec. Like hydroxyzine, cetirizine is an H1 receptor antagonist.
A key difference is cetirizine’s reduced ability to cross the blood-brain barrier. This explains why cetirizine causes less sedation and is marketed as a non-drowsy antihistamine, unlike hydroxyzine’s more pronounced sedative and anxiolytic effects.