Methoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER - prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox's relative IC50 at 19 mmol L-1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.
- MeSH
- Epinephrine * MeSH
- Receptors, Adrenergic MeSH
- Endonucleases MeSH
- Humans MeSH
- Methoxamine MeSH
- DNA Repair * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Keywords
- NEO-SYNEPHRINE, GUTRON,
- MeSH
- Humans MeSH
- Methoxamine pharmacology adverse effects therapeutic use MeSH
- Norepinephrine MeSH
- Registries MeSH
- Check Tag
- Humans MeSH
- MeSH
- Alprostadil pharmacology MeSH
- Dinoprostone pharmacology MeSH
- Rats MeSH
- Methoxamine pharmacology MeSH
- Serotonin physiology metabolism MeSH
- Tachyphylaxis MeSH
- In Vitro Techniques MeSH
- Vasoconstriction drug effects MeSH
- Hindlimb blood supply metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- MeSH
- Behavior, Animal drug effects MeSH
- Cystamine MeSH
- Rats MeSH
- Methoxamine MeSH
- Check Tag
- Rats MeSH
