Metixene (hydrochloride hydrate)

Metixene is an antagonist of muscarinic acetylcholine receptors (mAChRs; K_i = 15 nM for the rat receptor).¹ It also inhibits bovine acetylcholinesterase (AChE) by 43% when used at the concentration 10 µM and butyrylcholinesterase (BChE; IC₅₀ = 1.6 µM for the horse enzyme) in cell-free assays.² Metixene reduces the proliferation of P388 leukemia and doxorubicin-resistant P388 (P388/ADR) cells (EC₅₀s = 10 and 12 µM, respectively).³ It induces apoptosis in BT474 and MDA-MB-231 breast cancer cells when used at a concentration of 15 µM and induces autophagy in the same cells at 10 µM.⁴ In vivo, metixene (1 mg/kg three times per week) decreases tumor weight and volume and improves survival in an MDA-MB-231 breast cancer mouse xenograft model.

WARNING This product is not for human or veterinary use.

1. Syvälahti, E.K., Kunelius, R., and Laurén, L. Effects of antiparkinsonian drugs on muscarinic receptor binding in rat brain, heart and lung. Pharmacol. Toxicol. 62(2), 90-94 (1988).

2. Tasso, B., Catto, M., Nicolotti, O., et al. Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer’s disease. Eur. J. Med. Chem. 46(4), 2170-2184 (2011).

3. Ramu, A., and Ramu, N. Reversal of multidrug resistance by phenothiazines and structurally related compounds. Cancer Chemother. Pharmacol. 30(3), 165-173 (1992).

4. Fares, J., Petrosyan, E., Konojia, D., et al. Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases. J. Clin. Invest. e161142 (2023).