Dextromethorphan and Bupropion as an anti-addictive agents

[dopamimetic]

Okay, it's not the most obvious example and it can become addictive itself. But DXM addiction isn't as severe when compared to opioids or crack, and it becomes interesting when you look at the pharmacology:

(–)-18-Methoxycoronaridine (18-MC) is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemist Martin E. Kuehne from the University of Vermont. In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose.[1] [2] 18-MC is a α3β4 nicotinic antagonist and, in contrast to ibogaine, has no affinity at the α4β2 subtype nor at NMDA-channels nor at the serotonin transporter,[3] and has significantly reduced affinity for sodium channels and for the σ receptor, but retains modest affinity for μ-opioid receptors where it acts as an antagonist,[4] and κ-opioid receptors.[5] The sites of action in the brain include the medial habenula, interpeduncular nucleus,[6][7][8] dorsolateral tegmentum and basolateral amygdala.[9] It has also been shown to produce anorectic effects in obese rats, most likely due to the same actions on the reward system which underlie its anti-addictive effects against drug addiction.[10]

Dextromethorphan and Bupropion antagonise the same receptor. Okay, methadone too, this makes it all a bit more complicated. I'm really curious why methadone is so addicting when it's a NMDA AND α4β2 antagonist - maybe the potency is too low?

 

[serotonin2A]

The answer probably is that these nicotinic mechanisms have some efficacy but they are far from a magic bullet. Bupropion certainly can help people wean themselves off of nicotine but it doesn't ameliorate all addiction. Methadone is a full mu agonist and it's nicotinic actions and weak NMDA blockade do not fully block the signaling changes that induce tolerance and dependence.