Coke + Dopamine β-hydroxylase inhibitors.

[rse]

I very like doing cocaine IV in pretty moderate doses. But this drug is always frustrates me every time due to short time of action and extreme hypertension that comes after the main "dopamine" effect fade out. Basically I very liked mephedropne IV before, that worked like magic and almost not having any problems, while with coke I got uncomfortable hypertension after the main effect. I duuno why but looks like mephedrone has it's own hypotension properties that makes the experience very smooth, or maybe it's because of the serotonin, which cocaine lacks.

While I study some info I think this happens because large portion of dopamine being converted down to norepinerphine and gets you unpleasant hypertension for about 1-2 hrs after until this gets cleaned. I've already tried to combine coke with lyrica which definately helps but not much. Also I've seen people using low doses of A-blockers like clonidine, but never tied yet. Actually this only deals with the native epinephrine release, but I belive cannot deal with those have been created from the dopamine breakdown.
So, I go and search for the enzyme that doing this and looks like it's -Dopamine β-hydroxylase. So I was thinking what if using a bit of the inhibitor like Fusaric acid or Disulfiram is a potent dopamine β-hydroxylase inhibitor. I'm thinking if this working it's also can potentiate and prolongate the cocaine high while blocking the unwanted effects. Does anyone tried it ? Is it safe to use?

 

[Skorpio]

Fusaric acid looks to have a lot of nonspecific toxicity towards cells. I wouldn't take it for any reason at this point. Disulfram seems like a bad choice, as it would make you unable to have any alcohol with cocaine, which is like a peanut butter cup without chocolate.

Furthermore, cocaine is pleasurable not because it has any special affinity for dopamine receptors, but because of its relatively balanced effects on dopamine, serotonin, and norepinephrine.

Enhancing only the dopamine affinity will likely make it more compulsive without providing greater euphoria.

 

[rse]

Hm, I usually not doing alcohol with coke, also I was searching the med papers about Disulfiram and looks like it's indeed potentiates the cocaine hight and also increasing it's half-life by 2+. But also, increasing the blood pressure and heart rate.

https://www.sciencedirect.com/science/article/pii/S0006322397005064?ref=cra_js_challenge&fr=RR-1

 

[negrogesic]

and looks like it's indeed potentiates the cocaine hight and also increasing it's half-life by 2+. But also, increasing the blood pressure and heart rate.

https://www.sciencedirect.com/science/article/pii/S0006322397005064?ref=cra_js_challenge&fr=RR-1

And anxiety.

By simultaneously slowing elimination and altering cocaine's DA:NE:5HT balance (which is quite magical and unique) you may just wind up stimulated and anxious for a longer period of time rather than euphoric.

NE is a good thing. At least in part, and for a while

Disulfiram Attenuates Drug-Primed Reinstatement of Cocaine Seeking via Inhibition of Dopamine β-Hydroxylase - Neuropsychopharmacology

The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive ‘Antabuse reaction’ that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use...

www.nature.com

 

[rse]

NE is a good thing. At least in part, and for a while

Yes, a good thing, in small amounts, but coke increasing it too much, while using IV for about 150-200mg it's getting only problems. The similar drug mephedrone which I prefer 10 times better increasing it in a waay lesser amounts and allows to do almost any amounts IV and feels 10 times better without any problems. But unfortunately I don't have access to it right now.

 

[negrogesic]

Yes, a good thing, in small amounts, but coke increasing it too much, while using IV for about 150-200mg it's getting only problems. The similar drug mephedrone which I prefer 10 times better increasing it in a waay lesser amounts and allows to do almost any amounts IV and feels 10 times better without any problems. But unfortunately I don't have access to it right now.

If you are injecting it, I'd say disulfiram would be a pretty strong no go since the best part of IV cocaine is that rush (which stems from that special balance of rapid monoamine reuptake inhibition). Diminishing the available NE would diminish that rush substantially.

This is a good summary of the impacts of disulfiram on the qualitative effects of cocaine in humans:

To understand how disulfiram treatment affects an individual’s response to cocaine, and to shed light on the mechanism driving the drop in cocaine intake, a series of human laboratory studies looked at whether disulfiram influences the self-reported subjective effects of cocaine. The results have been conflicting. Two groups reported no difference in the subjective effects of cocaine, such as cravings or high, using a “Yes/No” scale (3) or a visual analog scale (47). Another group reported a modest, non-significant increase in “high” and “anxiety” (48), whereas others found increases in nervousness, paranoia (49, 50), or psychosis (51, 52). Two other studies report decreased “rush,” “high,” or “craving” (44, 53). Disulfiram is also reported to enhance some subjective effects of the psychostimulant dextroamphetamine, including “high,” anxiety, “bad drug effects,” “craving,” and “drug liking” (54). The modulation of subjective effects by disulfiram may in fact vary, increasing or decreasing the rewarding effects of cocaine; the most consistent finding is a worsening of the aversive effects of cocaine, such as anxiety and paranoia. Other side effects of disulfiram clinical trials on cocaine dependence are headaches, fatigue, and paranoia (55). Thus, there may be a “disulfiram-cocaine” reaction that is similar to but distinct from the “disulfiram-alcohol” reaction and that promotes cocaine abstinence.

Mechanisms of Disulfiram-induced Cocaine Abstinence: Antabuse and Cocaine Relapse

The anti-alcoholism drug disulfiram (Antabuse), which is an inhibitor of aldehyde dehydrogenase, induces an aversive reaction to alcohol consumption and thereby helps patients reduce alcohol intake. Recent clinical trials, ...

www.ncbi.nlm.nih.gov

If anything you'd want to find something that perhaps slows elimination of cocaine without interfering with its pharmacodynamic properties. That said, I'm not aware of anything that can accomplish this in a meaningful way. Maybe chew/quid some coca flour while using IV cocaine your normal way?

 

[rse]

If you are injecting it, I'd say disulfiram would be a pretty strong no go since the best part of IV cocaine is that rush (which stems from that special balance of rapid monoamine reuptake inhibition).

I highly doubt that Disulfiram can kill the cc rush completely (I think only elephant doses of tranks can) even with degreased NE it should be crazy enough. Anyway, the NE ruining the overall experience for me, so I'd rather have less crazy rush than this. Meph for example don't have this crazy NE rush, but still feeling better than that (mostly because of serotonin rush supress the NE a lot I guess - for my feeling the cc completly lacks off serotonin or having very mild effect on it thats totally overwhelmed by NE and DA sometimes I shoot Es and it's very similar to meph due to sert rush - but E lacks the dopamine for me, so the meph is like having best of dopamine and sert). As for the Disulfiram the reports said that subjective changes are quite small. However, I'm more interested in that increase of the duration and concentration. Maybe I just can use 50℅-70% of my standard shot and get near the same level of high or slight lower but while having more duration time.
The most strange thing is that hypertension effects comes only when the fun is over, no matter how strong the initial rush has been, I can run and jump around without any problems for the first 15 minutes it basically starting when the main effect is off. Then I just lying down on the bed feeling like 90 y.o. good thing is this state is usually goes off in 2 hrs to complete normal. Anyway I was going to try clonidine also.

 

[negrogesic]

I highly doubt that Disulfiram can kill the cc rush completely (I think only elephant doses of tranks can) even with degreased NE it should be crazy enough. Anyway, the NE ruining the overall experience for me, so I'd rather have less crazy rush than this. Meph for example don't have this crazy NE rush, but still feeling better than that (mostly because of serotonin rush supress the NE a lot I guess - for my feeling the cc completly lacks off serotonin or having very mild effect on it thats totally overwhelmed by NE and DA sometimes I shoot Es and it's very similar to meph due to sert rush - but E lacks the dopamine for me, so the meph is like having best of dopamine and sert). As for the Disulfiram the reports said that subjective changes are quite small. However, I'm more interested in that increase of the duration and concentration. Maybe I just can use 50℅-70% of my standard shot and get near the same level of high or slight lower but while having more duration time.
The most strange thing is that hypertension effects comes only when the fun is over, no matter how strong the initial rush has been, I can run and jump around without any problems for the first 15 minutes it basically starting when the main effect is off. Then I just lying down on the bed feeling like 90 y.o. good thing is this state is usually goes off in 2 hrs to complete normal. Anyway I was going to try clonidine also.

I mean you could try it, the combination probably won't kill you (then again perhaps it could given the associated increasd in heart rate and blood pressure when compared to cocaine alone).

But I don't think you'll find what you're looking for with this combo unfortunately.