Posted by SLS on May 11, 2000, at 10:26:51
In reply to Re: SEROQUEL? Sulpiride experience..., posted by KarenB on May 9, 2000, at 11:31:34
Hi Karen.
> I think - and Andrew or one of those guys can correct me if I'm wrong - that Mirapex is supposed to be the closest thing to Sulpiride, chemically, on our shores. I may be giving this a try soon.
Mirapex can certainly produce the same end-results as sulpiride.
Mirapex (pramipexole) is a drug that helps to excite dopaminergic neurons by attaching itself directly to the postsynaptic receptors and stimulating them, thus causing this neuron to fire and send the message on to the next neuron. Mirapex is considered to be an agonist of the receptor. Sulpiride and amisulpride excite dopaminergic neurons in a different way. These drugs, too, bind directly to dopamine receptors. However, they do not stimulate them. While they remain attached to the receptor, they prevent dopamine from stimulating it. Sulpiride and amisulpride are considered to be antagonists of the receptor. The neuron is prevented from “seeing” dopamine. When the presynaptic neuron is convinced that there is not enough dopamine floating around in the synaptic cleft (the gap between the presynaptic and postsynaptic neuron), it makes more and releases more. The increase in the amount of dopamine in the synaptic cleft results in the attachment of dopamine to more postsynaptic receptors, stimulating the nerve to fire more often.Of course, both sulpiride and amisulpride block those dopamine receptors located on the postsynaptic neuron as well. This tends to prevent it from firing. For this reason, these two drugs, considered neuroleptics, are used as antipsychotics. However, sulpiride and amisulpride, unlike the other antipsychotics, bind much, much more strongly to presynaptic receptors than they do to postsynaptic receptors. When used at low dosages, many more presynaptic receptors are blocked (resulting in more dopamine being released) than are postsynaptic receptors. This may be the reason why these two drugs exert antidepressant effects at low dosages, and antipsychotic effects at high dosages.
Some of the other neuroleptics may produce an antidepressant effect, in part, by the same mechanism. If neither sulpiride nor amisulpride are available, Zyprexa and Seroquel might be good choices to try as a substitute.
Amineptine promotes the stimulation of dopaminergic neurons in yet a third way. It prevents the released dopamine from being retrieved by the presynaptic neuron so that it can be used again. Amineptine inhibits the reuptake of dopamine and is thus labeled a reuptake inhibitor. The concentration of dopamine within the synaptic cleft increases, thereby inducing the postsynaptic neuron to fire.
These drugs, when combined, probably act synergistically to promote a prolonged increase in the activity of dopaminergic neurons. On paper, the combination of sulpiride or amisulpride with amineptine is brilliant. Surely, the person who thought of it must be. It is my hope that mazindol (Mazinor), another dopamine reuptake inhibitor, may serve as a substitute for amineptine in these combinations. Unfortunately, things that look good on paper don’t always pan-out.
- Scott
poster:SLS
thread:32846
URL: http://www.dr-bob.org/babble/20000508/msgs/33182.html