Posted by SLS on May 15, 2000, at 17:36:12
In reply to Re: Amineptine substitute? Peter, COMT inhibitor, posted by AndrewB on May 15, 2000, at 9:12:34
> Thanks Peter. I'll ask KarenB how she compares adderall with amineptine.
>
> Any reason to think a COMT inhibitor like Entacapone acts like amineptine? Entacapone increases dopamine in the synaptic cleft. It seems it may able to help people with depression and yet it can cause anxiety in some. Amineptine can relieve depression yet increase anxiety.--------------------------------------------------------------
Hi Andrew.
I spent some time earlier today looking into the pharmacology of various psychostimulants. It's hard to find one that would be similar enough to amineptine to choose as a candidate to replace it. If the idea is simply to look for a drug to increase the concentration of dopamine within the synaptic cleft, they are all eligible. Obviously, this property is not in and of itself sufficient to promote a long-lasting antidepressant effect.The one thing that differentiates amineptine from the stimulants is that it lacks the ability to increase the release dopamine into the synaptic cleft. Perhaps the property of stimulants to release dopamine explains why tolerance to their stimulating effects occurs and why their antidepressant effects are usually transient when used monotherapeutically.
In the mid 1980's, a drug named nomifensine (Merital) was marketed briefly as an antidepressant. It had been studied for many years, and its pharmacology was well documented. It worked well for many people. To my knowledge, it was the only other antidepressant besides amineptine that was a potent reuptake inhibitor of dopamine as well as being a norepinephrine reuptake inhibitor. Like amineptine, nomifensine does not increase the release of dopamine.
The only other marketed drug I could find that potently inhibits the reuptake of dopamine without promoting its release is mazindol. Mazindol also inhibits the reuptake of norepinephrine.
Amineptine, nomifensine, and mazindol have similar catecholaminergic pharmacological profiles and differ from stimulants and cocaine in that they do not promote the release of dopamine.
The inhibition of COMT in the synaptic cleft would spare dopamine, but it would not prevent this spared dopamine from being sucked back up by the presynaptic neuron, whereupon it is dismantled by MAO. In addition, the rate of reuptake would be increased, as the presynaptic neuron is induced to produce more transporter molecules. I think the inhibition of synaptic COMT would enhance dopaminergic neurotransmission, but not to the extent as would amineptine, nomifensine, or mazindol. It still might work, though. It is difficult to predict.
What have you found regarding the efficacy of entacapone as an antidepressant?
The few things that I've run across weren't too impressive. It makes a good adjunctive medication for treating Parkinson's Disease by prolonging the effect of levodopa, primarily through the inhibition of its break-down in the blood stream. I don't know to what degree COMT inhibition within the neuronal synapse influences the concentration of neurotransmitter there.
You mentioned that you didn't feel mazindol would make a good candidate to replace amineptine in the role of an augmenting agent to amisulpride due to its potential to produce anxiety. How does mazindol compare to the stimulants with regard to the incidence and magnitude of anxiety as a side effect?
Do you know of anyone who has added a stimulant to amisulpride, sulpiride, or Zyprexa?
- Scott
poster:SLS
thread:33419
URL: http://www.dr-bob.org/babble/20000508/msgs/33509.html