| Class | Noradrenergic antidepressant |
|---|---|
| Chemistry |
Tetracyclic piperazinoazepine |
| Routes of administration |
Oral only |
| Absorption |
Rapidly and completely absorbed; 30% oral bioavailability due to a considerable first-pass effect |
| Solubility |
pKa 6.92; soluble in both water and alcohol |
| Distribution |
VOD=15.7L/kg; 90% protein bound |
| Metabolism |
Hepatic metabolism by aromatic hydroxylation, N-oxidation and N-demethylation. |
| Elimination |
70% of the metabolites are renally excreted; the rest in the bile |
| Time course of action |
Elimination half-life 10-17 hrs |
| Target receptor |
Presynaptic α-adrenoceptors and histamine receptors in the CNS, as wel as the NET reuptake transporter |
| Mechanism of action |
The mechanism of antidepressant effect is thought to be the inhibition of presynaptic control of noradrenaline release (i.e. it does the oposite of what clonidine does). Also, it inhibits reuptake of noradrenaline. |
| Clinical effects |
Sedation, fluid retention, loss or gain of weight, vertigo; risk of serotonin syndrome with overdose |
| Literature reference |
Brogden et al (1978) |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |