The Sound of Evolution
Amitriptyline
Mechanism of action:
Amitriptyline is a tricyclic antidepressant (TCA). Its mechanism of action is not fully understood, but it is thought to inhibit the reuptake of norepinephrine and serotonin at presynaptic nerve terminals, thereby increasing the concentration of these neurotransmitters in the synaptic cleft and enhancing their activity in the central nervous system. This, in turn, affects neural pathways involved in mood regulation and pain modulation. Amitriptyline may also antagonize multiple receptors, including histamine H₁ receptors, muscarinic acetylcholine receptors, and α₁-adrenergic receptors.
Reference(s):
1. Grauer MT et al. (2004). P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood brain barrier in mice after a 10-day administration of amitriptyline. J Psychopharmacol.
2. O'Brien FE et al. (2013). Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability. Int J Neuropsychopharmacol.
3. Abaut AY et al. (2007). Oral bioavailability and intestinal secretion of amitriptyline: Role of P-glycoprotein? Int J Pharm.