I NUK3D U
Bluelighter
Could it have something to do with intracranial pressure; and the release thereof?
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N&PD Moderators: Skorpio | someguyontheinternet
Various dopaminergic drugs
- Thread starter polymath
- Start date
tyrael
Bluelighter
I've only just started checking out the ADD thread (finally got my knowledge up to the point where I'm able to understand what's going on! 
), so I just want to start by thanking you guys! 
Extremely informative and interesting posts here!!
+1 for Domperidone. I would say the best anti-emetic I've had (obviously no rec. value)
), so I just want to start by thanking you guys! Extremely informative and interesting posts here!!+1 for Domperidone. I would say the best anti-emetic I've had (obviously no rec. value)
polymath
Bluelight Crew
Opioid-induced nausea is very similar to motion sickness, while amphetamine has been used as a motion sickness medication... Anyone know whether amphetamine's antiemetic action in those cases is a CNS effect or caused by lessening of inner ear's sensitivity?
In regards to emesis, there are a whole host of receptors/sites invovled (various nACh receptor sites, 5-HT3, adrenergic, Yet-2Bdiscovergic etc, etc).
Sturnam
Bluelighter
- Joined
- Aug 12, 2008
- Messages
- 738
I found a recent article talking about how heterodimers of dopamine receptors (D1 and D2 in this case) mediate the functional selectivity of some dopaminergic drugs.
Here's the article:
http://www.ncbi.nlm.nih.gov/pubmed/21785426
Here's the article:
http://www.ncbi.nlm.nih.gov/pubmed/21785426
Not sure if this is the right place for this, but it does relate to the original post inasmuch as modafinil is a dopaminergic drug. Although its exact mechanisms of action are not clear, modafinil has been used experimentally in treating cocaine dependence as it appears to reduce the euphoria from cocaine (A double-blind, placebo-controlled trial of modafinil for cocaine dependence, Dackis CA et al. Neuropsychopharmacology 30 (1): 205–11). My question is, given that the t1/2 of modafinil is 15 hours, wouldn't daily dosing with it reduce the euphoria of cocaine whilst it was still in the system?
helium-4
Bluelight Crew
This may be a bit off topic from the OP, but still with the title...
Anyone have experience with dopamine agonists like pramipexole or ropinirole in combination with amphetamine? I didn't really notice to much with difference in amphetamine with pramipexole, even when compulsive behavior became apparent (no increase in amphetamine consumption), besides a bit of tiredness/decrease in stimulation from the amphetamine which began before the adaption period was over, starting before the impulsiveness becoming a serious side-effect. With ropinirole I've found lower doses of amphetamine to be very anxiety producing even with a nice anti-depressant effect from the ropinirole. At higher doses I do not receive anywhere as close to as much anxiety as seen with lower doses. When I've raised the ropinirole doses, I did notice an increase desire to redose and dose high with amphetamines, even with minimal impulsiveness in other areas. Pleasure from masterbating orgasms was seen to be higher on ropinirole than pramipexole, especially as I raised the dose of ropinirole. I was more apathetic on pramipexole than ropinirole as well. Both pramipexole and ropinirole have strong increase in sedation of alcohol, but minimal increase in pleasure or sedation from kratom.
I'm also curious as to how RLS dopamine agonist would effect nmda-antagonist. With DXM, the intoxication intensity would increase with both, but can't really honestly tell if there was an increase or decrease in euphoric properties with either tried dopamine agonist.
Anyone have experience with dopamine agonists like pramipexole or ropinirole in combination with amphetamine? I didn't really notice to much with difference in amphetamine with pramipexole, even when compulsive behavior became apparent (no increase in amphetamine consumption), besides a bit of tiredness/decrease in stimulation from the amphetamine which began before the adaption period was over, starting before the impulsiveness becoming a serious side-effect. With ropinirole I've found lower doses of amphetamine to be very anxiety producing even with a nice anti-depressant effect from the ropinirole. At higher doses I do not receive anywhere as close to as much anxiety as seen with lower doses. When I've raised the ropinirole doses, I did notice an increase desire to redose and dose high with amphetamines, even with minimal impulsiveness in other areas. Pleasure from masterbating orgasms was seen to be higher on ropinirole than pramipexole, especially as I raised the dose of ropinirole. I was more apathetic on pramipexole than ropinirole as well. Both pramipexole and ropinirole have strong increase in sedation of alcohol, but minimal increase in pleasure or sedation from kratom.
I'm also curious as to how RLS dopamine agonist would effect nmda-antagonist. With DXM, the intoxication intensity would increase with both, but can't really honestly tell if there was an increase or decrease in euphoric properties with either tried dopamine agonist.
Hammilton
Bluelighter
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- Sep 2, 2008
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I've not noticed much impulsiveness from pramipexole, which I currently take .5mg. Perhaps a bit hypersexual, not incredibly so though. Certainly not enough that I'd stop taking it.
Personally, I'm more worried about motor side effects than anything. My left eye doesn't want to open right after I close it, and if I look over my shoulder (like I'm backing up a car) a muscle that feels like it connects near my jaw bone to the side of my mouth doesn't want to release, it feels like it 'clicks' five or six times and goes back to normal strangely. It started just on my left side maybe 4 days ago, and yesterday it started on the right side. Occupationally I have to drive backwards a lot, so it's something I notice a lot.
I'm wondering if it's really a side effect of the drug, or if it's a withdrawal effect because about an hour after I take the drug I can't even make it happen on purpose, but as the day wears on and I'm approaching the 24-hour-since-last-dose mark there's no need to provoke it, it happens rather readily.
Tell you what, though, forgetting to take a dose makes my RLS about a trillion times worse. I wonder if someone who didn't have RLS took it for a while they'd experience it upon withdrawal.
It is a good mood elevator, and doesn't provoke mania (or if it does, it hasn't in me) unlike virtually every other antidepressant I've ever taken.
Personally, I'm more worried about motor side effects than anything. My left eye doesn't want to open right after I close it, and if I look over my shoulder (like I'm backing up a car) a muscle that feels like it connects near my jaw bone to the side of my mouth doesn't want to release, it feels like it 'clicks' five or six times and goes back to normal strangely. It started just on my left side maybe 4 days ago, and yesterday it started on the right side. Occupationally I have to drive backwards a lot, so it's something I notice a lot.
I'm wondering if it's really a side effect of the drug, or if it's a withdrawal effect because about an hour after I take the drug I can't even make it happen on purpose, but as the day wears on and I'm approaching the 24-hour-since-last-dose mark there's no need to provoke it, it happens rather readily.
Tell you what, though, forgetting to take a dose makes my RLS about a trillion times worse. I wonder if someone who didn't have RLS took it for a while they'd experience it upon withdrawal.
It is a good mood elevator, and doesn't provoke mania (or if it does, it hasn't in me) unlike virtually every other antidepressant I've ever taken.
NeuroPsyence
Bluelighter
- Joined
- Apr 30, 2011
- Messages
- 76
Their action with regard to dopamine is primarily as inhibitors of its reuptake, although they interact with the D2 receptor in subtle ways as well. Neither acts as a releasing agent of dopamine fyi.
BilZ0r
Bluelight Crew
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- Messages
- 6,675
Interesting post. Something I've always wondered about. I suspect there are lots of factors going on here.
1) Don't underestimate pharmacokinetics. A "stimulant" like drug needs to come on quickly for it to be found amusing.
2) It appears to me that purely dopaminergic reuptake inhibitors are not actually very fun. This reminds of how pure serotonin releases are less amusing than mixed 5-HT/NA/DA releasers.
3) None of your dopamine agonists are mixed, well, apomorphine is relatively non selective... but it could hardly be seen as a general agonist (poor D1 affinity). Adding to the mix you've got the idea of agonist directed trafficking... maybe none of these artificial agonists traffic down the right pathways?
So... lets just rule out direct agonists. We have amphetamines (fun), cocaine (fun), and L-dopa (you say not fun). I put it to you, that a lot of people do find L-Dopa moderately nice. Of course, you have the issue of getting enough L-DOPA into someones system without peripheral problems. Also, it is worth considering, where is the dopamine being released by L-DOPA (as you rightly wondered). If you do full dopaminergic lesions to an animal, L-DOPA still causes a big increase in brain dopamine. However, cocaine and amphetamine don't do anything. So it seems likely that L-DOPA is being converted willy nilly around the brain, and potentially interacting with other monoamine receptors (my memory tells me dopamine is pretty good agonist at alpha2 receptors for instance). A similar question is why are SSRIs and MDMA so different?
But basically, my guess at your questions goes like this cocaine and amphetamine rapidly rise in the brain post-ingestion. This cause release (you know what I mean) of dopamine solely around dopaminergic terminals, and real dopamine activates D1-D5 receptors in the correct ratio (Remember dopmaine has different affinity for these receptors). Finally, coke and amphets cause a co-increase in 5-HT and NA, which enhances pleasurably.
Hit me up with a PM, or I probably wont check this thread again.
1) Don't underestimate pharmacokinetics. A "stimulant" like drug needs to come on quickly for it to be found amusing.
2) It appears to me that purely dopaminergic reuptake inhibitors are not actually very fun. This reminds of how pure serotonin releases are less amusing than mixed 5-HT/NA/DA releasers.
3) None of your dopamine agonists are mixed, well, apomorphine is relatively non selective... but it could hardly be seen as a general agonist (poor D1 affinity). Adding to the mix you've got the idea of agonist directed trafficking... maybe none of these artificial agonists traffic down the right pathways?
So... lets just rule out direct agonists. We have amphetamines (fun), cocaine (fun), and L-dopa (you say not fun). I put it to you, that a lot of people do find L-Dopa moderately nice. Of course, you have the issue of getting enough L-DOPA into someones system without peripheral problems. Also, it is worth considering, where is the dopamine being released by L-DOPA (as you rightly wondered). If you do full dopaminergic lesions to an animal, L-DOPA still causes a big increase in brain dopamine. However, cocaine and amphetamine don't do anything. So it seems likely that L-DOPA is being converted willy nilly around the brain, and potentially interacting with other monoamine receptors (my memory tells me dopamine is pretty good agonist at alpha2 receptors for instance). A similar question is why are SSRIs and MDMA so different?
But basically, my guess at your questions goes like this cocaine and amphetamine rapidly rise in the brain post-ingestion. This cause release (you know what I mean) of dopamine solely around dopaminergic terminals, and real dopamine activates D1-D5 receptors in the correct ratio (Remember dopmaine has different affinity for these receptors). Finally, coke and amphets cause a co-increase in 5-HT and NA, which enhances pleasurably.
Hit me up with a PM, or I probably wont check this thread again.
greenberryhaze
Bluelighter
I've never had any nausea from dopaminergic stimulants, even at very high doses. The opposite, actually; I've used amphetamine as a hangover cure.
helium-4
Bluelight Crew
Meant to post another reply in this thread but got lazy.
Anyway, so I had to stop using ropinirole after a week or so of use. I started to get some very concerning side-effects. I started to become very achy and had muscle pains. In a location where I had a catheter surgery back in April, which occasionally still hurts, started to become painful enough to make walking up stairs an annoyance and sitting down in a chair bothersome. I was also getting sharp pain in locations that were seemingly random - areas where I haven't injured myself or stressed. The ropinirole also gave me constipation and pain in my intestinal track, which I have had serious problems with in the recent past (was in the hospital with my colon completely inflamed in April). In combination with kratom one night, this pain became very concerning and lasted hours.
Not sure why, but I started to take the pramipexole again after stopping the ropinirole. The side-effects previously seen with the initial week and half period of pramipexole were for the most part not seen. I was still compulsively eating, but I wasn't as drowsy, didn't get an apathetic mind set, and wasn't to noticeably more impulsive than I already am. it's anti-depressant effects were also stronger, but more impressively, it took away my social anxiety issues as good if not better than ketamine. The effects on socialability still continues to this day, two weeks after the last time I dosed any, which is even more impressive. One problem out side of the slight increase in some impulsive behaviors was that the ability to provide relief from RLS wasn't as significant/decreased a decent amount. I'm tempted to refill my script and start it up again, as I'm thinking I didn't give the adaption period enough time, and the amphetamine use might have had some interaction with these dopamine agonists. Could the aches and pains while on ropinirole been a result of amphetamine and the ropinirole creating vasoconstriction outside of what is seen with amphetamine alone? One thing about this is I didn't notice any real discoloration on the skin, or headaches. Was the adaption time for the initial pramipexole drawn out longer from amphetamine use? Also since stopping the dopamine agonists my tolerance for amphetamine seems higher than normal, especially with a two and half week break in between amphetamine use. During use of the dopamine agonists with amphetamine, my tolerance for amphetamine seemed to not increase very much with some higher doses thrown in. I could take 15mg and feel like I took 30-45mg of amphetamine at once but with out as much stimulation (my normal daily dose is 15mg twice a day). I guess really I'd need to take the dopamine agonists with out amphetamine to see if there is any difference.
I also found music to be more pleasurable while on the dopamine agonists, and women to be more compellingly beautiful. I'd get a very rewarding feeling just seeing a beautiful women. Was quite interesting, as I'm already a little hypersexual and deal with sexual frustration issues, and the feelings experienced didn't increase the intensity of those problems.
I'm going to see a neurologist about my RLS problems in two weeks as my doc felt he couldn't do anything or prescribe me anything else (not even while I wait for my doc appointment, he told me he can't prescribe anything else for sleep with the amphetamine script...). I may wait to try pramipexole till after that visit, but I do really like the effect on my social ability. It seriously has such a significant effect that I kinda just want to use it for that purpose.
Anyway, so I had to stop using ropinirole after a week or so of use. I started to get some very concerning side-effects. I started to become very achy and had muscle pains. In a location where I had a catheter surgery back in April, which occasionally still hurts, started to become painful enough to make walking up stairs an annoyance and sitting down in a chair bothersome. I was also getting sharp pain in locations that were seemingly random - areas where I haven't injured myself or stressed. The ropinirole also gave me constipation and pain in my intestinal track, which I have had serious problems with in the recent past (was in the hospital with my colon completely inflamed in April). In combination with kratom one night, this pain became very concerning and lasted hours.
Not sure why, but I started to take the pramipexole again after stopping the ropinirole. The side-effects previously seen with the initial week and half period of pramipexole were for the most part not seen. I was still compulsively eating, but I wasn't as drowsy, didn't get an apathetic mind set, and wasn't to noticeably more impulsive than I already am. it's anti-depressant effects were also stronger, but more impressively, it took away my social anxiety issues as good if not better than ketamine. The effects on socialability still continues to this day, two weeks after the last time I dosed any, which is even more impressive. One problem out side of the slight increase in some impulsive behaviors was that the ability to provide relief from RLS wasn't as significant/decreased a decent amount. I'm tempted to refill my script and start it up again, as I'm thinking I didn't give the adaption period enough time, and the amphetamine use might have had some interaction with these dopamine agonists. Could the aches and pains while on ropinirole been a result of amphetamine and the ropinirole creating vasoconstriction outside of what is seen with amphetamine alone? One thing about this is I didn't notice any real discoloration on the skin, or headaches. Was the adaption time for the initial pramipexole drawn out longer from amphetamine use? Also since stopping the dopamine agonists my tolerance for amphetamine seems higher than normal, especially with a two and half week break in between amphetamine use. During use of the dopamine agonists with amphetamine, my tolerance for amphetamine seemed to not increase very much with some higher doses thrown in. I could take 15mg and feel like I took 30-45mg of amphetamine at once but with out as much stimulation (my normal daily dose is 15mg twice a day). I guess really I'd need to take the dopamine agonists with out amphetamine to see if there is any difference.
I also found music to be more pleasurable while on the dopamine agonists, and women to be more compellingly beautiful. I'd get a very rewarding feeling just seeing a beautiful women. Was quite interesting, as I'm already a little hypersexual and deal with sexual frustration issues, and the feelings experienced didn't increase the intensity of those problems.
I'm going to see a neurologist about my RLS problems in two weeks as my doc felt he couldn't do anything or prescribe me anything else (not even while I wait for my doc appointment, he told me he can't prescribe anything else for sleep with the amphetamine script...). I may wait to try pramipexole till after that visit, but I do really like the effect on my social ability. It seriously has such a significant effect that I kinda just want to use it for that purpose.
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helium-4
Bluelight Crew
http://www.geriatrie-online.at/mm/mm004/2007_Willeit_PHNO_Amphetamine.pdf
So maybe there is some truth to the potential for interaction between amphetamine and both pramipexole and ropinirole. Seems a long adaption period might make sense with this study.
So maybe there is some truth to the potential for interaction between amphetamine and both pramipexole and ropinirole. Seems a long adaption period might make sense with this study.
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