polymath
Bluelight Crew
- Joined
- Nov 4, 2010
- Messages
- 1,884
Hello,
found this some time ago: https://en.wikipedia.org/wiki/SKF-81,297
Seeing from this that selective direct dopamine agonists can have a psychostimulant effect like amphetamine, I got the idea that maybe a D1 selective partial agonist could be like "buprenorphine of stimulants", which would simply stop having effect if abused, instead of making you able to stay awake for a week and end up in the psych ward...
A plant alkaloid stepholidine is thought to be a D1 partial agonist and D2 full antagonist, and seems to have some anti-addictive effects. See the link below.
https://www.ncbi.nlm.nih.gov/pubmed/24145772
There's some problems with this though - some paper claimed that stepholidine is actually a full antagonist at D1 too. Also, some D1 agonists seem to act through a different secondary messenger than SKF-81,297 and not produce a stimulant effect (similarly like some 5HT2A agonists are not hallucinogenic).
What do you think would happen if someone ingested aripiprazole (which blocks D2 and D3 receptors but leaves D1 free) and then took a non-specific dopamine enhancer like L-DOPA on top of that? Could the combination act like a selective D1 agonist? Of course this is not a valid reason to take an antipsychotic unless you already know for certain that they don't cause akathisia/dyskinesias/MNS to you, and the L-DOPA can also cause peripheral side effects because it's also converted to dopamine and norepinephrine outside the CNS, so don't take this idea too seriously. :D
found this some time ago: https://en.wikipedia.org/wiki/SKF-81,297
SKF-81,297 is a synthetic drug of the benzazepine chemical class that acts as a selective dopamine D1/D5 receptor full agonist, and produces a characteristic stimulant-like pattern of anorexia, hyperactivity and self-administration in animals.[1] This profile is shared with several related drugs such as 6-Br-APB and SKF-82,958,[2] but not with certain other D1 full agonists such as A-77,636, reflecting functional selectivity of D1 activation.[3][4][5] Newer findings reveal that SKF-81,297 additionally acts as a partial agonist at D1-D2 receptor heteromers.[6]
Seeing from this that selective direct dopamine agonists can have a psychostimulant effect like amphetamine, I got the idea that maybe a D1 selective partial agonist could be like "buprenorphine of stimulants", which would simply stop having effect if abused, instead of making you able to stay awake for a week and end up in the psych ward...
A plant alkaloid stepholidine is thought to be a D1 partial agonist and D2 full antagonist, and seems to have some anti-addictive effects. See the link below.
https://www.ncbi.nlm.nih.gov/pubmed/24145772
There's some problems with this though - some paper claimed that stepholidine is actually a full antagonist at D1 too. Also, some D1 agonists seem to act through a different secondary messenger than SKF-81,297 and not produce a stimulant effect (similarly like some 5HT2A agonists are not hallucinogenic).
What do you think would happen if someone ingested aripiprazole (which blocks D2 and D3 receptors but leaves D1 free) and then took a non-specific dopamine enhancer like L-DOPA on top of that? Could the combination act like a selective D1 agonist? Of course this is not a valid reason to take an antipsychotic unless you already know for certain that they don't cause akathisia/dyskinesias/MNS to you, and the L-DOPA can also cause peripheral side effects because it's also converted to dopamine and norepinephrine outside the CNS, so don't take this idea too seriously. :D