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Re: ritanserin, pimavanserin, and lumateperone

Posted by linkadge on September 21, 2021, at 18:18:44

In reply to Re: ritanserin, pimavanserin, and lumateperone, posted by undopaminergic on September 20, 2021, at 8:20:30

>If it inhibits the noradrenaline transporter >through some alternative binding site, wouldn't it >inhibit the tyramine pressor effect?

From my understanding there are differences in the peripheral and central noradrenergic systems. Centrally, I think there are two versions of the norepinephrine transporter NET-1 and NET-2. Hypertension can be mediated centrally or peripherally or both. Also, not every NET inhibitor is equally potent at all sites in the brain. There may also be allosteric sites. Similar to serotonin reuptake, some of the SSRIs more potently inhibit SERT at certain sites vs. other sites. For example paroxetine and escitalopram don't bind to the exact same sites of the serotonin transporter. Escitalopram also binds to an allosteric site of the serotonin transporter (a secondary binding site).

Here's an in-vivo PET study (in primates) showing that effexor is essentially a 'balanced' SERT / NET inhibitor.




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