Neuron Regeneration

[mad_scientist]

I believe there are therapies on the horizon, some of which may involve ibogaine, that attempt to "trick" the brain into thinking that there were never dopamine surpluses in the first place, so it senses the dopamine deficit and reverse-neuroadaptation takes place much faster.

Yeah the ibogaine derivative 18-methoxycoronaridine was in phase 2 clinical trials as an anti-addictive drug in humans a while back, been no news on it for some time though. Developed by a Dr Stanley Glick in the US somewhere.

The mechanism is selective antagonist action at alpha3 beta4 nicotinic acetylcholine receptors, and some of his other work demonstrated that any alpha3 beta4 antagonists can exert the same type of anti-addictive effects (he tested ibogaine, 18MC, dextromethorphan, mecamylamine and bupropion, all of which block alpha3 beta4 receptors to some extent). The effects of coadministration were synergistic, so i don't see why a combination product of dextromethorphan, mecamylamine and bupropion shouldn't have similar anti-addictive potential.

A similar mechanism is found in the new anti-smoking drug varenicline, which is an alpha4 beta2 partial agonist and alpha3 beta4 antagonist. Nicotinic pathways seem quite key to the establishment of physical changes in the brain that underlie addiction, so using the same pathways to reverse the changes is a sensible approach.

 

[Matt the Raver]

This probably needs a separate post, but what exactly is the connection between acetyl choline and dopamine?

 

[Psychedelics_r_best]

Well, I would only assume this so, but I suppose they coincide as acetyl choline often causes muscle responses, while dopamine stimulates energetic and motivational responses. I would then assume that the activities done in result of dopamine release would stimulate acetylcholine release.

 

[mad_scientist]

Dopamine-releasing neurons in the nucleus accumbens express acetylcholine receptors, presumably activation of alpha3 beta4 and alpha4 beta2 subtypes of AcH receptor on these neurons is involved in the structural changes that take place in chronic drug addiction. Hence why most adult drug addicts started out as teenage cigarette smokers, early use of nicotine primes the system for stronger drugs later on.

The whole system is all interlinked and very complicated!

Another example is the opiate receptors which are expressed on neurons which normally inhibit the action of the dopamine-releasing neurons, so when the first set of neurons are inhibited by opiates they stop inhibiting the second ones from releasing dopamine, hence there is a big dump of dopamine in the nucleus accumbens.

Anyway im no expert on this area, ask a molecular neuropharmacology lecturer for more details...