H1 Antihistamines

Introduction

• H₁ antihistamines competitively antagonise histamine at the H₁ receptor; they are the classical antiallergic agents ("antihistaminics"). Prototypes: diphenhydramine, chlorpheniramine, promethazine (first-generation) and cetirizine, loratadine, fexofenadine (second-generation).
• Histamine is a biogenic amine autacoid (β-imidazolylethylamine, a "local hormone") acting through four GPCR subtypes (H₁–H₄); H₁ antihistamines are selective for H₁ with negligible H₂/H₃ activity.
• Therapeutic rationale: they suppress the histamine-attributable component of immediate (type I) hypersensitivity — itch, wheal, flare, urticaria, rhinorrhoea — but do not block the antigen–antibody reaction itself, so the action is palliative, not curative.
• Milestones: antihistamine activity first shown by Bovet & Staub (1937); pyrilamine (mepyramine) the first clinically useful agent (1944). The H₁/H₂ classification was established by Ash & Schild (1966); James Black produced the first H₂ blocker (1972, Nobel 1988). First-generation agents date from the late 1930s; second-generation (less/non-sedating) agents arrived after 1980.