Amantadine Plus Ritalin

[Scarletta]

Does anyone know whether this combination would be synergistic or antagonistic?

Since amantadine is considered by many to be a dopamine agonist, (as well as an NDMA receptor antagonist), and ritalin is a dopamine reuptake inhibitor, I was thinking the possibility for synergy is there.

If the amantadine was taken before the ritalin, the amantadine would assist in the release of dopamine in a similar manner as an amphetamine would, and then later the ritalin would block the reuptake of the dopamine.

I had considered taking amantadine with adderall or dexedrine until I did research showing that the amantadine in effect competes with the amphetamine at the post-synaptic (I think it was) level...and then the subjective effects of the amphetamine are attenuated. (never mind the whole "taking amantadine/memantine to reduce amp tolerance" thing- not concerned about that here.)

Thanks for any comments!

 

[Riemann Zeta]

Amantadine has some nasty sides, I don't think that it is the kind of thing that you want to take every single day just to attempt potentiation of some methylphenidate.

 

[Scarletta]

Well, I've been prescribed Amantadine and took it for about a month. I didn't see much benefit with it so quit. Now I was just wondering if it was possible to combine with Ritalin, a drug I am on that I hopefully will get switched off of soon, since it seems so worthless, and wondering if there would be an improvement with the amantadine added to it. Not looking to potentiate it as it is since it seems so crappy. But would be interested if there would be a synergy from the amantadine that would improve the Ritalin effects.

 

[Holy_cow]

Since methylphenidate is pharmacologically similar to cocaine, this might answer your question:

Drug Alcohol Depend. 1988 Jul;21(3):195-202.

Amantadine: evaluation of reinforcing properties and effect on cocaine self-injection in baboons.

Sannerud CA, Griffiths RR.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

The ability of amantadine to maintain self-injection behavior and to alter self-administration of cocaine was examined in baboons using a standard intravenous cocaine self-injection procedure. Responding was maintained under a FR 80- or 160-response schedule of intravenous cocaine delivery (0.32 mg/kg per injection). Each drug injection was followed by a 3-h time-out allowing a maximum of 8 injections/day. Vehicle or amantadine doses were substituted for cocaine for a period of 15 or more days. Evaluation of a wide range of amantadine doses (0.32-32 mg/kg per injection) showed that this compound did not maintain self-administration behavior above vehicle control levels. In another experiment using the cocaine self-injection baseline, amantadine (10 or 32 mg/kg per day) was administered via a chronic intravenous infusion. Cocaine self-injection behavior was maintained and re-initiated during chronic amantadine exposure, suggesting that the reinforcing efficacy of cocaine was not modified by chronic amantadine administration.

PMID: 3168762 [PubMed - indexed for MEDLINE]

 

[Scarletta]

Thanks, Holy Cow, very helpful!

I took a look at some more studies. There were some indicating that in humans, after a 4 day dose of 100 mg two times a day of Amantadine, when cocaine was administered, the euphoria was enhanced. Whereas after one dose of 200 mg Amandtadine, the cocaine euphoria was attenuated or diminished.

There were also studies in rats showing that a dose of 150 mg/kg (HUGE) was enough to attentuate the locomotive effects of several stimulants such as d-amphetamine, caffeine, methylphenidate, and others. A dose of 10 mg/kg did not affect the locomotion caused by any of these at all. Even a dose of 50 mg/kg was able to attenuate caffeine and d-amphetamine and some others, but not as many of the drugs as the 150 mg/kg dose did. Interestingly, no dose of amantadine was able to diminish the euphoric and some other effects of morphine.

This seems to support a theory that the effects of amantadine are very dose dependent. High doses in rats (and the single high dose of 200 mg in humans) attenuated significantly the effects of most stimulants. A low dose of 10 mg/kg in rats (which is slightly more than the recommended equivalent dose a person would have) did not do anything, just as chronic (4 day) administration of 100 mg twice a day in humans did not attenuate, but actually increased, the euphoric effects of cocaine.

I guess there's only one way for me to find out. Probably take my amantadine prescription as directed, which is 100 mg twice a day, 12 hours apart. Wait about 4 days, then take some Ritalin and see what happens!

 

[elfspice]

perhaps amantadine is a partial dopamine agonist in fact? this would explain it's seeming paradoxical effects. also it could be competitive for receptor sites, and with long term dosing causing a sensitisation/upregulation due to it's inhibitory effect, causing the receptors to increase their response/receptor site count due to a short term blocking effect caused directly by the amantadine binding to it, in effect causing a direct short term artificially caused downregulation of the dopamine receptors resulting in upregulation. long term moderate dosing would cause an overall increase in sensitivity given the assumption that the drug is only acting in its suppressive capacity for a few hours at most, and leaving the receptors with a gradually increasing sensitivity during the rest of the time.

if this is in fact the explanation for this seeming paradoxical behaviour then i would suggest that one would want to stagger the amantadine dosing and dosing of ritalin as by this theory the ritalin would be suppressed in its effect if taken in too close a temporal proximity to the amantadine. i can't really think of any way to ameliorate this problem except perhaps using a more acute dosing method for the amantadine (intranasal, intramuscular, and at lower dose rate to avoid the plasma level getting too high) in order to minimise the exposure time and thus time of direct inhibition of the effect of the ritalin.

i would think possibly the trick would be to dose the amantadine after the time of day one no longer needs the ritalin, say just after dinner, and again before bedtime (10-12pm) so that their direct interaction in the synapses is avoided yet the post-direct activity time the ritalin can be more effective.

 

[alkap555]

Be careful with amantadine....the side effects can be brutal and in rare cases it can cause organ damage if renal function is compromized..I would say not worth it.