Chemistry of Ibogaine

Recent studies have shown that the primary metabolite from Ibogaine itself interacts with numerous neuron receptor transporters and neuronal networks within the mobile network and in the activity of dopaminergic-dependent and independent modulation circuits. Ibogaine takes the brain activity back into a healthy balance.

Ibogaine actions are reported to reduce dopamine concentrations in the body. This is evidenced by the presence of dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in larger quantities after Ibogaine administration.

This action of Ibogaine is to reverse the impact of drug abuse of some highly addictive drugs, i.e.

Name:

* Cocaine

* Morphine

* Amphetamines

* Crack cocaine

* Nicotine

* Alcohol

All these drugs act on dopamine dopaminergic systems and stimulate the body.

Ibogaine is a tryptamine. It has two separate chiral centers, meaning that there are four different stereoisomers of ibogaine. These four isomers are difficult to resolve.

Synthesis

One recent total synthesis of ibogaine and related drugs starts with 2-iodo-4-methoxyaniline which is reacted with triethyl((4-(triethylsilyl)but-3-yn-1-yl)oxy)silane using palladium acetate in DMF to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and then fluoride to form 2-(2-iodo-1H-indol-3-yl)ethanol. This is treated with iodine, triphenyl phosphine, and imidazole to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then, using 7-ethyl-2-azabicyclo[2.2.2]oct-5-ene and cesium carbonate in acetonitrile, the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclo[2.2.2]oct-5-ene is obtained. Using palladium acetate in DMF, the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclo[2.2.2]octane system in ibogaine is replaced with an endo ethyl, then epiibogaine is formed.

Crystalline ibogaine hydrochloride is typically produced by semi-synthesis from voacangine in commercial laboratories.

Derivatives

A synthetic derivative of ibogaine, 18-methoxycoronaridine (18-MC), is a selective α3β4 antagonist that was developed collaboratively by the neurologist Stanley D. Glick (Albany) and the chemist Martin E. Kuehne (Vermont). This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine such as coronaridine and voacangine that showed these compounds also have anti-addictive properties.