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Combining drugs that have the same mechanism of action...

A

airdusters

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Sep 22, 2016
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So lets say I have 250mg of propylhexedrine and 60mg of amphetamine salts (adderall)
These drugs both act as TAAR1 agonists that "reverse the transporters for dopamine, norepinephrine and serotonin, leading to a release of monoamines from presynaptic vesicles into the synaptic cleft."

Now my question is as follows: Do drugs with the same mechanism of action always produce a synergistic effect or do they "fight" over who gets to agonize the receptors?
Would it be wasteful or ineffective to combine them both?

How about 2mg alprazolam + 2mg lorazepam or 2mg of clonazepam?
 
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They will fight for occupancy of the same receptor sites. Synergy only happens when multiple mechanisms work together, such as SRI & NRI reuptake, but not usually two SRI mechanisms.
 
if the drugs have the same effect and same mechanism the result should be equal to an increase in dosage...2 mg alprazolam plus 2 mg lorazepam should be similar to 4 mg of alprazolam or lorazepam which is called additive synergy because the total effect is the sum of the two, while in true synergy the total effect is greater than the sum of the two effects, as you could have if two drugs have the same downstream effect via two different mechanism
 
IDK OP WHAT DO YOU THINK. TAKE ADDERALL AND COCAINE at once (NOT SRS) SEE IF THEY JUST "REPLACE" EACHOTHER.
 
xbandit07x said:
IDK OP WHAT DO YOU THINK. TAKE ADDERALL AND COCAINE at once (NOT SRS) SEE IF THEY JUST "REPLACE" EACHOTHER.
Click to expand...

Cocaine and Adderall (amphetamine) are not the same mechanism of action, one is reuptake inhibitor and one is phosphorylating releaser; so they block eachother: nothing additive about one another, in-fact just the opposite
 
Yeah but actually you can inhibit the reiptake of extra Dopamine using a methylphenidate and lets say Dex combo if Timed correctly with methylphenidate taken first.
 
Drugs "syngergise" when differing effects work together to create a new feeling. When they hit the same targets the effect can either be additive, or diminished, depending on efficacy and efficiency. If neither of the drugs are saturating the drug targets(receptors, transporters) then it is more likely to be additive, but if the targets are saturated by the more efficacious drug then the affects will be diminished by the lesser ligand competing for the same receptors/transporters.

But generally in practice the ligand with the higher binding affinity is going to bind to all the receptors/transporters it wants to whether is it more efficacious or not, and the drug with the lower binding affinity will only be able to act on the open targets. Which is why you won't get an additive effect with Bupe and Heroin unless the dose of bupe is VERY small, or while methadone can have an additive effect at low doses but a blocking effect at high doses, and SSRI's block MDMA.
 
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Nagelfar said:
Cocaine and Adderall (amphetamine) are not the same mechanism of action, one is reuptake inhibitor and one is phosphorylating releaser; so they block eachother: nothing additive about one another, in-fact just the opposite
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Do you think, given small enough doses of each, that the effect could be additive, theoretically?
 
i think not because amphetamine needs to enter neurons trough DAT in order to exert his effects and if it's blocked by cocaine less amphetamine will be uptake...maybe if you do the coke after the amphetamine but i doubt it will work...i remember one time doing coke while on mdma and it made me more lucid for about an half hour like attenuating the mdma rolling
 
I can see that, because of coke blocking the serotonin transporter, but I'm talking about sub-threshold doses of each, if you were full on rolling I imagine all your transporters were full. I mean what if you were to dose each drug so the blood levels were just below each of their EC50.
 
the benzos all have varying affinities for the benzodiazepine subunits. For instance, alprazolam acts largely on a2/a3 while clonazepam would have more hypnotic action, likely due to a1. If you're combining GABA allosteric modulators with GABA orthosteric modulators you're asking for an overdose.
 
Thank you for answering my questions Coolwhip and Ho-Chi-Minh. Also thanks Keif for moving my topic to the appropriate section.
 
on this topic

reboxetine with buproion?

Two NA based drugs, but one an NRI and the other, affecting NA in some way.

Feasible?
 
xbandit07x said:
Yeah but actually you can inhibit the reiptake of extra Dopamine using a methylphenidate and lets say Dex combo if Timed correctly with methylphenidate taken first.
Click to expand...

Doesn't matter which is "taken first", MPH blocks AMP from being taken into the transporters and thus the vesicules; blocking phosphorylation; amphetamine reverse transport if the transporter is phosphorylized first, is blocked by the re-uptake ligand association by the MPH or cocaine. Either way dampens the effects. I'll try to find a publishing or two to show this.
 
I don't think people realize how quickly monoamines clear the synapses, either through re-uptake or metabolization. I think people get this idea of RI's and RA's pumping out monoamines, getting metabolized, and the extra DA/NE hanging around for hours. Basically as soon as the drug is gone things go back to normal(relatively speaking). The only way timing would matter is if my above theory held true, which I'm not sure that it does, and you are talking about dosing one as the others affect is almost gone.
 
Amphetamines taken After cocaine or methylphenidate do not block it.

You can get a therapeutic reaction from Methylphenidate and 2 hours later amphetamine.

Cocaine and then adderall afterward would overstimulate you into a seizure or paranoia.

Cocaine at night when adderall was taken during the day, isn't as unsafe but has no additive and still don't.
 
xbandit07x said:
Amphetamines taken After cocaine or methylphenidate do not block it.
Click to expand...

They compete and phosphorylation is occupied mutually exclusively and lasts longer in association than high occupancy re-uptake ligands of shorter duration, when I have time I'll show the paper that showed the stats on it going both ways
 
So I took 6mg of alprazolam 10mg of clonazepam and 4mg of lorazepam around 5 hours ago. I think I might be immune to the sedative effects of BZDs. I just feel calm and clear headed. I've been taking 2mg of alprazolam twice a day for the last 2 months never abusing it.

I was kind of expecting to be annihilated. Didn't think this warranted a trip report so I thought I'd just make a quick post here.
 
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