Olza-5 Mechanism of Action

Pharmacology: The exact mechanism by which olanzapine exerts its antipsychotic effect is unknown. However, this effect may be mediated through a combination of dopamine and serotonin 5-HT₂ antagonism. Olanzapine is a selective monoaminergic antagonist with a strong affinity for serotonin 5-HT_2A and 5-HT_2C receptors and dopamine D₁, D₂, D₃, D₄ receptors. Olanzapine binds weakly to γ-aminobutyric acid type A (GABA_A), benzodiazepine (BZD), and β-adrenergic receptors. Olanzapine's high affinity binding to, and antagonism of, muscarinic M₁, M₂, M₃, M₄ and M₅ receptors may explain its anticholinergic effects. Olanzapine also binds with high affinity to histamine H₁ and α₁-adrenergic receptors. Antagonism of histamine H₁ and α₁-adrenergic receptors may be responsible for the occurrence of somnolence and orthostatic hypotension, respectively, seen with olanzapine use.
Pharmacokinetics: Absorption: Systemic - Well absorbed. Food effects none.
Distribution: Systemic - Vd: 1,000 L.
Metabolism: Systemic - Hepatic: via CYP1A2 and CYP2D6.
Excretion: Systemic - Fecal: 30%, Renal: 57%.
Elimination: Half-life: Systemic - 30 hrs (range 21 to 54 hrs).