Variation in the Affinity of Amitriptyline for Muscarine Receptor Subtypes

Abstract

The affinity of amitriptyline for muscarine M₁ receptors was studied in the rat cerebral cortex and rabbit vas deferens utilizing binding studies as well as inhibition of carbachol-induced phosphoinositide hydrolysis in the cerebral cortex and blockade of the muscarinic prejunctional inhibition of sympathetic nerve stimulation in the rabbit vas deferens. The inhibition constants (K₁) or dissociation constants (K_b) obtained were approximately 6- to 20-fold lower than those obtained at muscarine M₂ receptors in rat atria (binding and negative inotropic response) indicating that amitriptyline exhibits a degree of muscarine M₁ receptor selectivity.

Randomised clinical trial: the effects of amitriptyline on drinking capacity and symptoms in patients with functional dyspepsia, a double-blind placebo-controlled study

“…Nausea and other prodromal symptoms are centrally generated by the satiety centre in the forebrain (amygdala and insula) after activation of the nucleus tractus solatarius (via the hypothalamus) 40, 41 . AMT may influence the afferent pathway involved in this central regulation of nausea, as an antagonist of the muscarinic receptors and histamine H1 receptors 42–45 . However, the exact working mechanism of AMT and its effect on nausea remain unclear.…”

Analysis of the effects of a tricyclic antidepressant on secondary sleep disturbance induced by chronic pain in a preclinical model

“…Amitriptyline has several mechanisms of action, such as serotonin receptor antagonism, adrenalin α 1 receptor antagonism, histamine-1 receptor antagonism, muscarine-1 receptor antagonism, and sodium channel blocker [17][18][19][20]. There is a possibility that these mechanisms directly improve sleep, especially of 5-hydroxytryptamine 2A (5-HT 2A ) receptor antagonism by amitriptyline.…”

Segmental Spinal Root Avulsion in the Adult Rat: A Model To Study Avulsion Injury Pain

“…Amitriptyline and carbamazepine are proposed to block tetrodotoxin (TTX)-resistant sodium channels, 13,14 and carbamazepine is the drug of choice for pain relief associated with another neuropathic condition, trigeminal neuralgia, in which the trigeminal root is often compressed. 15 Amitriptyline has other sites of action within the central nervous system (CNS) including inhibition of N-methyl-d-aspartate (NMDA), 16 neurokinin (NK)1, 17 and aminergic 18 and acetylcholine receptors, 19,20 while increasing spontaneous glycine release. 21 Other more drastic approaches to intractable pain management include surgical ablation of nervous tissue by DREZotomy.…”