Mono-amine oxidase inhibitor

Dennis J. McKenna, G. H. N. Towers, and F. S. Abbott. "Mono-amine oxidase inhibitors in South American hallucinogenic plants Tryptamine and B-carboline constituents of Ayahuasca". Journal of Ethnopharmacology 10 (1984) 195-223. 

The placement of the methyl group between the two carbons (so to speak) produces a cyclopropyl system. The simplest example is 2-phenylcyclopropyl-amine, a drug with the generic name of tranylcypromine and the trade name Parnate. It is a mono-amine oxidase inhibitor and has been marketed as an antidepressant,... 

Mclsaac. W.M. Estevez, V. 1966. Stmcture-action relationships of /3-carbolines as mono-amine oxidase inhibitors. Biochemical Pharmacology Vol. 26 1625-1627. 

Hodgson CA, Propofol and mono-amine oxidase inhibitors. Anaesthesia (1992) 47,356. 

MAO-inhibitors are chemical compounds whose activity in the body slows down or interferes with Mono Amine Oxidase, an enzyme system that oxidizes many compounds in foods and drugs into harmless byproducts. In the presence of MAO-inhibitors, compounds that would normally be metabolized into inactive by-products instead have the duration of their physiological and psychological activity extended. 

The ayahuasca potion is made of two plants, one of which reassembles double-helical vines. Ayahuasca contains the psychoactive chemicals DMT and several harmaline alkaloids. DMT can be extracted and smoked with powerful effect. However, eating DMT does little because MAO (mono-amine oxidase) in our guts deactivates the DMT when DMT is taken orally. On the other hand, the alkaloids in ayahuasca inhibit MAO in the gut, so that the brew is psychoactive. I wonder how the indigenous peoples of the Amazon ever figured out what plants from the thousands of plants in the forest to combine to get both the DMT and the MAO-inhibitor. 

A dose of 1 at 30 mg/kg increased the effects of intravenous doses of epinephrine at 5 g/kg and of dl-noreplnephrine at 10 ug/kg on both blood flow and blood pressure. Intravenous phenoxybenzamine at 15 mg/kg plus tolazollne at 2 mg/kg prevented almost completely the actions of I on blood pressure and blood flow Intravenous reserpine at 2 mg/kg increased markedly the effects of I at 30 mg/kg on blood pressure and peripheral resistance, but converted the usual immediate, small, temporary increase in blood flow into an immediate, small, temporary decrease. These various responses would be expected from either a mild sympathomimetic amine or an inhibitor of the breakdown of endogenous catecholamines Indeed, I at 10 M, was found to inhibit the monoamlneoxldase of the rat s liver. If the dose of I used in these experiments were distributed into the same fraction of the body water as that estimated for the human body,the concentration in the plasma would be about 9 times that stated above as the effective concentration for inhibiting the mono amine oxIdase. It is possible that inhibition of monoamlneoxldase by I plays a part in inducing the effects of the oxime on blood vessels and blood pressure. It is possible also that I interferes with reuptake of catecholamines by nerve endings this possibility seems not to have been explored. 

In this chapter, we discuss the synthetic methodologies used to prepare fluoroolefins and present examples of mechanism-based inhibitors of amine oxidases, r-aminobutyric acid transaminase and S-adenosylhomocysteine hydrolase which incorporate this structural functionality. Ve have restricted our discussion to the syntheses of terminal mono-, di- and trifluoroolefins, omitting the large body of synthetic endeavour directed towards other fluoro olefins (4). 

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