farmacista
Bluelighter
binding values are more a measure of the affinity for the transporter, while potency is better described by reuptake inhibition, efficacy is defined as the maximal effect that a drug can induce in functional studies
N&PD Moderators: Skorpio | someguyontheinternet
Cocaine is thought to act like an "inverse agonist" at DAT. Binding studies provide one measure of potency for interacting with DAT, but they don't address whether a ligand actually produces cocaine-like effects.
I don't really understand how the term inverse agonist can apply to a transporter like DAT in a way that would distinguish it from a normal antagonist. If the molecule is bound to the protein and thus preventing substrates from binding, I don't see how also lowering its activity makes any difference, given that's it's not actually able to perform any actions during that time.
The only variation on monoamine transport blockers I can imagine wouldn't have effects identical to antagonists would be a drug that binds to the transporter permanently as an irreversible inhibitor. I'm not sure such a substance even exists currently, nor if any studies have been done to explore the possibilities and effects of permanently disabling various transporter proteins.
Do you mean a releasing agent? Yes, in a way, that is what some of the evidence suggests. But cocaine does that in a way that is completely distinct from amphetamine and other releasers.But if it reverses the transporter, wouldn't that make cocaine a DRA rather than a reuptake inhibitor?
Absorption from blood to brain require that the molecule bears no charge so pKa VITAL
Distribution - The LogP governs how lipophilic the drugs (does it sit in watery blood or Fatty brain tissue.
Of course, you could RTFM yourself to learn this - or is this site devoted to those who can't to get those who can to do the work?
Cocaine is thought to act like an "inverse agonist" at DAT. Binding studies provide one measure of potency for interacting with DAT, but they don't address whether a ligand actually produces cocaine-like effects.
How does the effect of cocaine at DAT differ from that of amphetamine and its derivatives? What about NET and SERT? Its activity at SERT is particularly interesting, because if cocaine's effects are as some in this thread have suggested - and it essentially reverses the transport direction at DAT - having similar effects on SERT would make it (at least at first glance) not at all unlike MDMA and related compounds.
How does the effect of cocaine at DAT differ from that of amphetamine and its derivatives? What about NET and SERT? Its activity at SERT is particularly interesting, because if cocaine's effects are as some in this thread have suggested - and it essentially reverses the transport direction at DAT - having similar effects on SERT would make it (at least at first glance) not at all unlike MDMA and related compounds.
If so, it makes sense that pure cocaine should feel like a milder version of MDMA.
I wonder though, does a compound exist that acts as a reuptake inhibitor or releasing agent for DA and 5-HT but not NE?
Very nice WP pages indeed, I'll have to go through both of them in detail one day. Maybe a good idea is to look over all the structures and outline a summary of the SAR (e.g moiety X on carbon Y leads to ... ) and the overall pharmacophore of these sets of compounds.