Wait a minute. Abilify works both ways?

[deadendgame]

So abilify works as a dopamine agonist and antagonist. So technically if a meth addict was using abilify instead of meth, he could still get the same high?

 

[serotonin2A]

No. It's a partial agonist. It doesn't fully mimic dopamine, and it certainly doesn't have psuchostimulant effects.

 

[paranoid android]

So abilify works as a dopamine agonist and antagonist. So technically if a meth addict was using abilify instead of meth, he could still get the same high?

Yeah it's a partial agonist and certainly has no effect like Amphetamines, Cocaine or Methylphenidate. Even if it was a dopamine agonist like say Ropinirole (trade name Requip) or Pramipexole (Trade name Mirapex) both of which are used to treat Restless leg syndrome and Parkinsons that certainly does not mean that it has any Amphetamine type effects unless you count the possible psychosis these drugs can cause.

Bupropion is a Norepinephrine Dopamine reuptake inhibitor like Methylphenidate and Cocaine are but besides some very mild stimulation that may be the reason why it helps seasonal affective disorder it certainly acts nothing like Cocaine.

 

[dopamimetic]

Bupropion is a weird drug, it's NDRI properties are likely to be insignificant at used dosages, it only occupies around 20% of the transporters if I'm right ... but it modulates glutamate and nAChR's.. and Cocaine, Methylphenidate are probably DAT inverse agonists what makes them bypass the auto receptors and allow them to be equally potent as amphetamine.

But the dopamine agonist thing is right of course, they aren't stimulating really ... think it has something to do with constant agonism vs. firing pattern dependent agonism caused by 'real' DA?

So technically if a meth addict was using abilify instead of meth, he could still get the same high?

Even when he's using meth + abilify, it depends on the binding affinity of the latter, if the released DA is able to displace it or not. This is why buprenorphin users can't get high any more on other opioids.

 

[serotonin2A]

Bupropion is a weird drug, it's NDRI properties are likely to be insignificant at used dosages, it only occupies around 20% of the transporters if I'm right ..s.

I think calling 20% occupation insignificant is based on a misconception. The magnitude of a drug effect is based on occupancy and efficacy; you don't necessarily have to occupy most receptors to produce a significant effect. For example, lofentanil produces anesthesia at 25% mu receptor occupation. That means that high efficacy opioids probably produce analgesia at 10% occupation or even lower levels. Occupying 20% of available DAT would definitely have neurochemical consequences, and it is entirely possible that a relatively low % occupation could produce some types of therapeutic responses (at least for some drugs).


http://www.ncbi.nlm.nih.gov/pubmed/6135373

 

[Doctor.K]

I think calling 20% occupation insignificant is based on a misconception. The magnitude of a drug effect is based on occupancy and efficacy; you don't necessarily have to occupy most receptors to produce a significant effect. For example, lofentanil produces anesthesia at 25% mu receptor occupation. That means that high efficacy opioids probably produce analgesia at 10% occupation or even lower levels. Occupying 20% of available DAT would definitely have neurochemical consequences, and it is entirely possible that a relatively low % occupation could produce some types of therapeutic responses (at least for some drugs).


http://www.ncbi.nlm.nih.gov/pubmed/6135373

Good information and source, thank you, I learn something new everyday here.

 

[Memantine]

Aripiprazol is a D2 partial agonist with an intrinsinic activity of about 6% compared with dopamine. There is little benefit from this property other then reducing the risk of EPS and prolactin elevation. But it will certainly not make you euphoric.



Furthermore i think the reason why bupropion only occupys 20% DAT at clinical dosages(taken orally) is because bupropion has a bioavailibility of about 5%. It is quickly converted by CYP2B6 to active metabolites that are more selective for NET.

 

[Memantine]

Bupropion is a weird drug, it's NDRI properties are likely to be insignificant at used dosages, it only occupies around 20% of the transporters if I'm right ... but it modulates glutamate and nAChR's.. and Cocaine, Methylphenidate are probably DAT inverse agonists what makes them bypass the auto receptors and allow them to be equally potent as amphetamine.

But the dopamine agonist thing is right of course, they aren't stimulating really ... think it has something to do with constant agonism vs. firing pattern dependent agonism caused by 'real' DA?

Even when he's using meth + abilify, it depends on the binding affinity of the latter, if the released DA is able to displace it or not. This is why buprenorphin users can't get high any more on other opioids.

What is the relationship between DAT inverse agonism and autoreceptor function? How do they bypass autoreceptors?