Histamine receptors mechanism of action

Role and effects of H1 histamine receptor blockers

Drugs affecting $H_1$ histamine receptors have the ability to cross the blood-brain barrier (BBB). Due to this, they exert a marked depressant effect on the central nervous system.

The main mechanism of their hypnotic and antiallergic action is as follows:

• Competitive blockade of $H_1$ receptors prevents the initiation of the calcium cascade and subsequent muscle contraction.
• Action on the central nervous system allows agents such as diphenhydramine and doxylamine to be used as effective hypnotics.

Doxylamine is particularly valued because it does not disrupt the natural physiological sleep architecture and has low toxicity.

Mechanisms of action of H2 blockers in gastroenterology

The second major group consists of $H_2$ histamine receptor blockers, which are considered one of the most effective and frequently used pharmacological groups in the treatment of acid-related conditions.

Pharmacodynamics: the drugs block the stimulatory effect of histamine released by enterochromaffin-like cells. This leads to the following outcomes:

• Daytime basal acid secretion at rest and between meals is reduced.
• Hydrochloric acid output during the nighttime is substantially decreased.
• Overall production of the enzyme pepsin is inhibited.

These properties make the drugs indispensable for controlling gastric juice acidity.

Combined blockade in antiemetic therapy

Certain compounds are capable of affecting multiple receptor types simultaneously, which expands the scope of their clinical application. A prime example is meclozine.

Its pharmacodynamics is based on combined blockade of:

1. Central $H_1$ histamine receptors.
2. Central $M_1$ cholinergic receptors.

Due to this dual mechanism, the drug is successfully used to eliminate vomiting of vestibular origin, including motion sickness and air sickness, as well as in radiation therapy. It is characterized by a rapid onset of action and a prolonged effect lasting about 24 hours.

Comparison with other antiallergic pathways

In the pharmacotherapy of allergic reactions, histamine receptor blockade is complemented by other targets in the inflammatory cascade:

• Anti-IgE therapy (e.g., omalizumab) interrupts the binding of free IgE to mast cell receptors, preventing sensitization.
• Membrane stabilizers (cromoglicic acid, nedocromil sodium) block mast cell degranulation.
• Leukotriene pathway blockers (montelukast, zafirlukast, zileuton) inhibit the effects of inflammatory mediators.
• Mixed-action drugs (ketotifen) combine the properties of a mast cell membrane stabilizer and an $H_1$ receptor blocker.

Class and exam questions

What else to study on this topic

• Pharmacokinetics of doxylamine and diphenhydramine
• Comparative characteristics of selective and non-selective antihistamines
• Role of leukotrienes in the inflammatory cascade
• Features of the use of 5-$HT_3$ serotonin receptor blockers in oncology
• Pharmacological profile of combined anticholinergics (Aeron)

Other topics in the «Drugs and Prescriptions» section

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