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Re: Norepinehprine D4 receptor

Posted by undopaminergic on June 1, 2020, at 6:37:28

In reply to Re: Norepinehprine D4 receptor undopaminergic, posted by linkadge on June 1, 2020, at 5:29:40

> >atomoxetine is a kappa opioid receptor antagonist
> Clarification - I believe it is an **agonist at the kappa receptor.

Right. That is what I meant. Good catch!

> Kappa agonism can cause dysphoria, which my be why atomoxetine failed as an antidepressant. Kappa antagonists (mirtazapine is a weak antagonist) have antidepressant properties.

The most potent clinically available kappa antagonist is buprenorphine, and it does have antidepressant properties, but it is also a partial mu agonist.

I read that kappa antagonism increases dopamine release in the prefrontal cortex.

> Dynorphin (a kappa agonist) is increased by stress and may be related to stress induced depression.

I also read it downregulates dopamine D2-receptors

> You're right that kappa agonists can produce depersonalization (akin to the drug salvorin-a in salvia). I actually liked salvia.

Did you enjoy it more at peak, or was it the "afterglow"?

Myself, I couldn't get any effect at all.

> There is some evidence that kappa agonists have anticonvulsant and anti-addictive properties.

They do reduce cocaine self-administration in rats. However, kappa *antagonists* reduce it even more! My hypothesis is that the agonists reduce drug reward (perhaps via downregulation of dopamine D2), and antagonists counteract drug tolerance (thus lower doses are needed).





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