Posted by J Kelly on May 24, 2016, at 21:56:44
In reply to Re: Dopamine antagonism » J Kelly, posted by SLS on May 24, 2016, at 7:05:46
> > > Hi, Jade.
> > >
> > > > Just so I'm clear, a dopamine antagonist (like Zyprexa) means less dopamine available, correct?
> > >
> > > A direct antagonist binds to a receptor and blocks it. It is not a reuptake inhibitor. In general, anything that binds to a receptor is called a ligand. Ligands are divided into categories, based upon their action at the receptor. Agonists stimulate, while antagonists and inverse agonists inhibit.
> > >
> > > As weird as this sounds, there is actually more dopamine available when using neuroleptic antipsychotics. This occurs because the drug binds to pre-synaptic receptors along with post-synaptic receptors. (Abilify might be an exception). The antagonism of the pre-synaptic receptors convinces the neuron to manufacture and release more dopamine. Although more dopamine is available, the antipsychotic prevents the post-synaptic neuron from "seeing" it because the receptors are blocked by the antagonist.
> > >
> > >
> > > - Scott
> > >
> >
> > Hi,
> >
> > So is it a wash then?
>
> No. Blocking the postsynaptic receptors prevents any dopamine from stimulating them, depending on the binding affinity (stickiness) of the drug, and its concentration.
>
> > Or does Zyprexa = less available/useable dopamine?
>
> Think of receptors as being polka-dots on the surface of the neuronal membrane. Each can be stimulated by an agonist or inhibited (blocked) by an antagonist. If most of the polka-dots are blocked by the attachment of a sticky antagonist, it doesn't matter how much dopamine is floating around. In a way, the receptors are acting like magnets. Dopamine and drug ligands are also like magnets. The stronger the magnet, the more difficult it is for another magnet to knock it off.
>
> Zyprexa is a molecule that acts as a ligand at dopamine receptors. The strength of the Zyprexa molecule's magnet (binding affinity), and how many molecules are competing for receptor occupancy help determine the dosage necessary for therapeutic effect.
>
> Why most antipsychotics increase the release of dopamine involves the blockade of presynaptic autoreceptors. If you block presynaptic receptors, the presynaptic neuron does not detect intrasynaptic dopamine, and is convinced that it must make and release more. However, it really doesn't matter how much of this released dopamine is available if the the postsynaptic receptors are blocked from binding it.
>
>
> - ScottThank you for explaining :)
Jade
poster:J Kelly
thread:1089116
URL: http://www.dr-bob.org/babble/20160501/msgs/1089196.html