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Medicines > fda max : 20 mg/d or 4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct) or 80 mg/d

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mechanism:
None (2) · Competitive antagonist at OX1R and OX2R. First-in-class DORA. Receptor dissociation slower than lemborexant or daridorexant. (1) · Highly β1-selective adrenergic antagonist. Greater selectivity than metoprolol or atenolol. (1) · Partial agonist at D2 and 5HT1A. Antagonist at 5HT2A, α1A, α1B, α2C. More potent 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism (relative to D2 partial agonism) than aripiprazole, proposed to reduce akathisia and enhance affective/cognitive effects. (1) · Selective inhibitor of PDE5. Slightly higher PDE5/PDE6 selectivity vs sildenafil (less visual side effect) but more PDE1 cross-activity (occasional QT effects at high doses). (1) · '"`UNIQ--vote-00000053-QINU`"' Also raises bradykinin, contributing to vasodilation and the characteristic dry cough. Renally cleared, unmetabolized; dose-adjust by eGFR'"`UNIQ--ref-00000054-QINU`"'. (1) · '"`UNIQ--vote-000003D1-QINU`"' SLCO1B1 polymorphism affects exposure but is most clinically actionable for simvastatin'"`UNIQ--ref-000003D2-QINU`"'. (1) · '"`UNIQ--vote-00000A1D-QINU`"' Like other ACE inhibitors, it raises bradykinin (driving the dry cough and rare angioedema). Renally cleared; dose-adjust in renal impairment'"`UNIQ--ref-00000A1E-QINU`"'. (1) · '"`UNIQ--vote-00000AEA-QINU`"' The 24-hour half-life supports once-daily dosing with consistent overnight BP control. Largely hepatically cleared (~98% biliary); no significant renal clearance dependence'"`UNIQ--ref-00000AEB-QINU`"'. (1) · '"`UNIQ--vote-0000111B-QINU`"' Intraoperative floppy iris syndrome is a recognized class effect. Recently emerging evidence (observational) suggests possible Parkinson's disease risk reduction via PGK1 binding — investigational and not a clinical indication'"`UNIQ--ref-0000111C-QINU`"'. (1)
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