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).
-undopaminergic
poster:undopaminergic
thread:1110375
URL: http://www.dr-bob.org/babble/20200511/msgs/1110432.html