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Re: Difference between an agonist and a releaser)

Posted by linkadge on December 24, 2009, at 10:46:57

In reply to Re: Difference between an agonist and a releaser) » linkadge, posted by West on December 24, 2009, at 8:23:00

There are a number of other ways to detect agonists (I'm not 100% sure how they work but some are based on..)

They can detect which receptors are agonized by binding the drug to a radioactive tracer and then seeing which areas of the brain it has affinity for. They can do it by cloning receptors (in vitro) and doing something with that.

They can also do it by behavioral tests or by seeing how the drug modifies the effects of other (better studied drugs) For instance, 5-ht1a agonists will produce hypothermia, 5-ht2a agonists will induce a head twitch response, 5-ht2 antaoninists block the effects of LSD etc.


>So there's no difference essentially, except in >the case of DA/SERT agonists, it's usually sub->receptors that are being forced to fire. Can you >get rebound depression from agonists in that >case?

Do you mean post-synaptic? Yeah, the presynpatic terminal will not release more neurotransmiter in response to a post-synaptic agonists *unless* the agonists has affinity for the presynaptic autoreceptor. Generally the autoreceptors control the release of a neurotransmitter.

Take buspar for instance, it is only a partial post synaptic 5-ht1a agonist but is a full presynaptic 5-ht1a autoreceptor agonist. This means that it will decrease the overall release of serotonin *and* produce the behavioral/neuroendocrine effects associated with activation of the post synaptic 5-ht1a receptors.

The argument with buspar is which action is more responsible for the anxiolytic effect.

Complicating maters further, long term administration of buspar may desensize the presynaptic autoreceptor rendering the serotonin release system less inhibited by serotonin - thus possible enhancing serotonin release in the long term.


The same holds for mirapex, I think. It has substantial affinity for presynaptic dopamine receptors too, so it may, over time enhance dopamine release in addition to agonizing post synaptic receptors.

In theory though, a selective (post synaptic) receptor agonist would not influence the release of a neurotransmitter.

Linkadge


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