trainman04
Bluelighter
- Joined
- Dec 18, 2017
- Messages
- 189
The occupancy of dopamine transporter (DAT) sites by bupropion and its metabolites in the human brain as measured by positron emission tomography was 26% according to GlaxoSmithKline researchers .
in any case, the above findings suggest that, although weak DAT occupation may occur, oral bupropion at clinically-used doses does not have the actual capacity to elevate dopamine levels in the human brain.[14] In accordance with this finding, based on analogy with serotonin reuptake inhibitors, higher than 50% inhibition of DAT would be needed for the dopamine reuptake mechanism to be a significant mechanism of the drug's action. Moreover, 65%75% DAT occupancy is necessary for euphoria and abuse potential.[82]
Ki values of sertraline at the human SERT, DAT, and NET of 0.29, 25, and 420 nM, respectively.[93] The selectivity of sertraline for the SERT over the DAT was 86-fold.[93] In any case, of the wide assortment of antidepressants assessed in the study, sertraline showed the highest affinity of them all for the DAT, even higher than the norepinephrinedopamine reuptake inhibitors (NDRIs) nomifensine (Ki = 56 nM) and BUPROPION (Ki = 520 nM).[93][104] Sertraline also has similar affinity for the DAT as the NDRI methylphenidate (Ki = 24 nM).[93][104] Tametraline (CP-24,441), a very close analogue of sertraline and the compound from which sertraline was originally derived, is an NDRI that was never marketed.[109]
So if wellbutrin alone is 27% on DAT and sertraline has higher affinity for dat than wellbutrin it should equal more than 50% if taken together thus block DAT efficiently and increase dopamine neurotransmission right and produce anti depressant effect? The text say sertraline has similar affinity for the DAT as the NDRI methylphenidate (ritalin).. I dont know how much that is .But the good thing with sertraline is its long half life 26 hours and ritalin has very short 7 hours or something similar. wellbutrin + sertraline block DAT to increase dopamine together they block over 50% dopamine transporter enough to produce an anti depressant effect im asking if i am correct if this makes sense would this work the way im thinking it would?
in any case, the above findings suggest that, although weak DAT occupation may occur, oral bupropion at clinically-used doses does not have the actual capacity to elevate dopamine levels in the human brain.[14] In accordance with this finding, based on analogy with serotonin reuptake inhibitors, higher than 50% inhibition of DAT would be needed for the dopamine reuptake mechanism to be a significant mechanism of the drug's action. Moreover, 65%75% DAT occupancy is necessary for euphoria and abuse potential.[82]
Ki values of sertraline at the human SERT, DAT, and NET of 0.29, 25, and 420 nM, respectively.[93] The selectivity of sertraline for the SERT over the DAT was 86-fold.[93] In any case, of the wide assortment of antidepressants assessed in the study, sertraline showed the highest affinity of them all for the DAT, even higher than the norepinephrinedopamine reuptake inhibitors (NDRIs) nomifensine (Ki = 56 nM) and BUPROPION (Ki = 520 nM).[93][104] Sertraline also has similar affinity for the DAT as the NDRI methylphenidate (Ki = 24 nM).[93][104] Tametraline (CP-24,441), a very close analogue of sertraline and the compound from which sertraline was originally derived, is an NDRI that was never marketed.[109]
So if wellbutrin alone is 27% on DAT and sertraline has higher affinity for dat than wellbutrin it should equal more than 50% if taken together thus block DAT efficiently and increase dopamine neurotransmission right and produce anti depressant effect? The text say sertraline has similar affinity for the DAT as the NDRI methylphenidate (ritalin).. I dont know how much that is .But the good thing with sertraline is its long half life 26 hours and ritalin has very short 7 hours or something similar. wellbutrin + sertraline block DAT to increase dopamine together they block over 50% dopamine transporter enough to produce an anti depressant effect im asking if i am correct if this makes sense would this work the way im thinking it would?
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