Amitriptyline (hydrochloride)

Amitriptyline is a first generation tricyclic antidepressant.¹ It inhibits serotonin (5-HT) uptake by isolated human platelets by 39 and 68% when used at concentrations of 1 and 4 µg/ml, respectively, and inhibits norepinephrine uptake in rat brain by 77% when administered at a dose of 10 mg/kg.^2,3 It is also an antagonist of the 5-HT receptor subtype 5-HT_2A (K_i = 20 nM), as well as histamine H₁, muscarinic acetylcholine, and α₁-adrenergic receptors (K_is = 1.1, 18, and 27 nM, respectively).^4,5,6 Amitriptyline (5-25 µM) prevents acid sphingomyelinase activation and subsequent ceramide release induced by infection with replication-deficient vesicular stomatitis virus pseudoviral particles (pp-VSV) presenting the severe acute respiratory coronavirus 2 (SARS-CoV-2) spike protein in Vero cells, an effect that can be overcome with exogenous application of C16 ceramide (Item No. 10681) or recombinant human acid sphingomyelinase.⁷ Formulations containing amitriptyline have been used in the treatment of depression and nerve pain. This product is also available as an analytical reference standard (Item Nos. 19029 | 19031).

WARNING This product is not for human or veterinary use.

1. Spencer, P.S. Review of the pharmacology of existing antidepressants. Br. J. Clin. Pharmacol. 4(Suppl 2), 57S-68S (1977).

2. Yates, C.M., Todrick, A., and Tait, A.C. Effect of imipramine and some analogues on the uptake of 5-hydroxytryptamine by human blood platelets in vitro. J. Pharm. Pharmacol. 16, 460-463 (1964).

3. Glowinski, J., and Axelrod, J. Inhibition of uptake of tritiated-noradrenaline in the intact rat brain by imipramine and structurally related compounds. Nature 204, 1318-1319 (1964).

4. Honda, M., Nishida, T., and Ono, H. Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT₂ receptors. Eur. J. Pharmacol. 458(1-2), 91-99 (2003).

5. Richelson, E., and Nelson, A. Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J. Pharmacol. Exp. Ther. 230(1), 94-102 (1984).

6. Cusack, B., Nelson, A., and Richelson, E. Binding of antidepressants to human brain receptors: Focus on newer generation compounds. Psychopharmacology (Berl.) 114(4), 559-565 (1994).

7. Carpinteiro, A., Edwards, M.J., Hoffmann, M., et al. Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells. Cell Rep. Med. 1(8), 100142 (2020).