Posted by SLS on January 20, 2006, at 6:57:53
In reply to Re: Which ADs increase DOPAMINE the most?, posted by linkadge on January 17, 2006, at 12:59:41
You are right (as usual)
> Thats a good question, and I don't know the answer. Two hypothesis would be the following:
> 1. Nardil has an effect on gaba metabolism. Gaba
> asserts an inhibitory controll over
> dopaminergic synapses.
In a normally functioning human brain, this is mostly true. However, it may be that some of us are wired a little differently such that GABA acts, through disinhibition, to increase the synthesis and release of dopamine or even opioids in a way similar to how some people react to alcohol or benzodiazepines. A minority of people become stimulated, aggressive, and hypersexual with these pro-GABAergic drugs.
> 2. Parnate is structurally related to
> amphetamine, (although it is debated as
> to whether parnate posesses any stimulant-like
> effect on dopamine release). There are case
> reports of Parnate abuse, whereas I don't know of any for Nardil.
When I was more vulnerable to self-medication, I tended to abuse Nardil more than Parnate because I found it gave me a reward kick shortly after taking it. Parnate has always left me with a persistent anhedonia which Nardil abolished when it worked.
The problem is this: I often see people here advise the choice of Parnate over Nardil when one is concerned about an imagined dopamine deficit syndrome. Yet, there is really nothing to their conceptualization of Parnate as being dopaminergic other than a vague notion of it having stimulant-like properties. As you point out, such properties represent a transient increase in the release and inhibition of reuptake of dopamine (and norepinephrine!). Yet, there is usually no mention of the tendency of this kind of chronic exposure to stimulants to produce depletions of DA stores rather than their replenishment. Another consideration is that a dose of Parnate is in and out of the body in 1-2 hours. (I don't know about its metabolites). If its effectiveness were dependent on the ability of Parnate to release DA, People would have to take it every 2 hours, or the antidepressant effect would not persist. But of course, it does. I believe that any DA release that Parnate might produce is not contributory to its efficacy as an antidepressant. If this were true, adding amphetamine to Nardil should be ubiquitously and immensely effective. To the best of my knowledge, it is not.
How do people know that they need dopamine in the first place?
Is a deficit in dopaminergic neural activity in reward and motivational centers of the brain the result of or the cause of depression? It does seem to be that the final pathways to the expression of depression are dopaminergic, but what has people so convinced that this is the primary site of pathology rather than a secondary downstream consequence of this pathology?