Posted by farshad on February 6, 2018, at 10:42:38
In reply to Re: whats a drug that blocks DAT(dopamind transporter), posted by SLS on February 6, 2018, at 9:11:02
> > > Methylphenidate
> > >
> > > (Ritalin, Concerta, Focalin)
> > >
> > > Generally, these are not good antidepressants.
> > >
> > > In my experience, DAT inhibition (dopamine reuptake inhibition) is not sufficient to effect antidepressant effects.
> > >
> > > Sertraline? I thought you wanted to avoid a SRI.
> > >
> > > Intestigational dopamine/norepinephrine reuptake inhibitor:
> > >
> > > Solriamfetol (jzp-110) DNRI: NDA submitted December, 2017
> > > Indicated for Excessive Sleepiness Associated with Narcolepsy and Obstructive Sleep Apnea. Parkinsons?
> > >
> > >
> > > - Scott
> >
> > My SERT is already pretty slow so
>
> You don't know that.
>
> > SSRI(sertraline in this case) wont make a difference for me for serotonin.
>
> You don't know that. Your statement here is in conflict with statements you have made previously.
>
> > But do you know if combining wellbutrin and sertraline together will block DAT enough to increase dopamine ?
> >
> > It says sertraline is stronger in blocking DAT than wellbutrin on wiki
>
> I looked up Ki on PDSP. Sertraline is a mild DAT inhibitor, which is stronger than bupropion.
>
> > .. So wellbutrin blocks DAT 27% , Sertraline say blocks 35% , thats enough for an effect right.
>
> Where did you get these numbers from? Do they provide values for other drugs? I question that bupropion is 27%. That sounds rather high to me. How do you know that the effects are simply additive? Perhaps the antidepressant effect is the result of some synergistism for other reasons.
>
> > They say you need to block atleast 50% to produce an anti depressant effect
>
> I would be interested to know where you found that.
>
> > thats why this combo is so common too.
>
> My *guess* is that adding bupropion to any SRI can work. My friend needs to take bupropion in combination with desvenlafaxine in order to achieve full remission.
>
> If you decide to commit to pro-dopamine mechanisms, you might try a combination of aripiprazole, lamotrigine, and buproprion.
>
>
> - Scott
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]
Tatsumi et al. (1997) found 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% and sertraline has higher affinity for dat than wellbutrin it should equal more than 50% if taken together thus produce an effect.
poster:farshad
thread:1096870
URL: http://www.dr-bob.org/babble/20161215/msgs/1096884.html