| Class | Monoamine reuptake inhibitor |
|---|---|
| Chemistry |
indole alkaloid extracted from Rauwolfia serpentine roots |
| Routes of administration |
Oral and IV |
| Absorption |
Rapid GI absorption, bioavailability 50-70% |
| Solubility |
Highly lipid soluble; penetrates the blood brain barrier. pKa = 6.6 |
| Distribution |
VOD unknown; presumably large, as it binds irreversibly to VMAT targets and to red blood cells |
| Metabolism |
Hepatic metabolism into inactive metabolites |
| Elimination |
Minimal renal clearance of unchanged drug; half-life of about 4-5 hours by distribution, but very long elimination half-life, ~ 160 hours |
| Time course of action |
Prolonged duration of effect due to irreversible binding |
| Target receptor |
VMAT-2 (vesicular monoamine transporter-2) |
| Mechanism of action |
Irreversibly blocks VMAT-2 in the adrenergic neurotransmission pathway. This results in catecholamines and serotonin lingering in the cytoplasm where they are destroyed by intraneuronal monoamine oxidase, thereby causing the depletion of catecholamine and serotonin stores in central and peripheral nerve terminals |
| Clinical effects |
Sedation, hypotension, bradycardia,depression. Can act an antipsychotic |
| Literature reference |
INCHEM article |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |