Hordenine

[Blue Druid]

Not sure if BDD is the place for this, if not apologies, go ahead & move it.

I'm trying to get some clarity around Hordenine (N,N-dimethyl-4-hydroxyphenylethylamine; N,N-dimethyl-tyramine) and its effects on MAO-B. I can't find much on the search other than some speculation that its an MAO-B Inhibitor (reversible or irreversible, who knows).

I've also seen it referred to as a "MAOB substrate" or "selective substrate for MAOB". What does substrate mean in this context? Is it just another way of saying its a selective MAO-B inhibitor? If so does anyone have any more info on this, eg whether its reversible or irreversible, whether it potentially inhibits MAOA too, comparison with other MAOB (I gather its a bit weaker than deprenyl) & any idea of effective dose?



Only research I can find is below & is a bit over my head, but am I right in thinking it doesn't result in vaso-constriction (in rats):

J Pharm Pharmacol. 1989 Jun;41(6):421-3.Links
Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.
Barwell CJ, Basma AN, Lafi MA, Leake LD.

School of Pharmacy, Portsmouth Polytechnic, Hampshire, UK.

The selectivity of the naturally occurring amine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 microM and maximum velocity of 128 nmol (mg protein)-1 h-1 compared with 144 microM and 482 nmol (mg protein)-1 h-1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 microM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.

 

[Tripman]

I'm moving this to advanced drug discussion.

They will be far superior at answering this than us.

 

[(zonk)]

If I'm not mistaken "substrate"simply refers to what enzyme is responsible for the compounds degradation and has nothing to do really with it's effect on MAO. So it may be a VERY weak inhibitor in the same sense that any compound which MAO-B eats would have some minor inhibition of that enzyme because it's making it busy I guess but maybe I'm wrong. I think the only reason there are publications going into detail about DMTyramine being an MAO-B substrate is that regular tyramine is a substrate for MAO-A and not B

 

[Blue Druid]

Thanks Zonk, so while it may be an MAO-B inhibitor (or may not) its not directly related to it being an MAOB substrate, just means its oxidised by MAOB.