Posted by Chairman_MAO on March 7, 2006, at 10:23:05
In reply to Preventing Tolerance to Dex/ DXM, Supplements, posted by temoigneur on March 6, 2006, at 23:36:21
(1) Non-competative NMDA antagonists: memantine, acamprosate (possibly taurine?), possibly amantadine?. Anecodatal evidence of efficacy, one human experiment into potentiation of methamphetamine effects by memantine. NMDA antagonists increase DA release; amantadine is probably inferior due to preference for striatal neurons in lieu of other relevant structures. Memantine 10-60mg/day in divided doses, amantadine 100-600mg/day in divided doses (risk of psychosis/cognitive impairment). See posts by AndrewB.
(2) Other NMDA antagonists: dextromethorphan (15-30mg qid) or dextromethorphan polistirex (30-60mg bid). Anecdotal efficacy. This is a dirty drug with a whole host of potential side effects and pharmacokinetic interactions. At the cough suppressant dose, it is benign IF YOU ARE NOT ON ANY DRUGS THAT INTERACT WITH IT. Do not combine this with MAOIs, bupropion, nefazodone, etc., etc. Ketamine: If you are thinking about using this then you already know more than I do about this subject. DO NOT COMBINE WITH DRUGS LISTED IN (1). DXM may raise blood levels of d-amphetamine through CYP450-2D6 inhibition.
(3) Magnesium/Zinc: See journal articles (look on pubmed) for dosages of each. Documented efficacy due to manifold effects, including possibly NMDA antagonism.
(4) Selegiline: Safest at MAO-B selective dosages (1.25-5mg po qd-tid). Prevents amphetamine, dopamine, and trace amine (notably PEA) catabolism by MAO-B. Has a tonic effect on catecholamine activity. Possesses neuroprotective/nootropic/anticonvulsant/stimulant/antioxidant/immunostimulant actions independent of MAO-B inhibition. DO NOT COMBINE WITH IRREVERSIBLE MAOIs (6). May be dangerous in combination with DEXTROMETHORPHAN (DXM).
(5) Moclobemide, brofaromine, toloxatone: other RIMAs: Slows NE and DA catabolism by MAO-A. Safer than irreversible MAOIs for this purpose (duration of action only lasts several hours). Do not combine with selegiline unless you are familiar with the risks of irreversible MAOIs (phenelzine, tranylcypromine, isocarboxazid). DO NOT COMBINE WITH (6).
(6) Irreversible, non-selective MAOIs: Reduces monoamine catabolism by MAO-A & MAO-B; reduces trace amine/amphetamine catabolism by MAO-B. Dramatic rise in intrasynaptic monoamine concentrations. MAO-A inhibition results in greater amount of store NE and SE available for release. Documented efficacy--even in very dire cases of depression. Possibility of hypertensive crisis *very real* but generally oprobably will not but certainlyverstated. D-amphetamine is often used to counteract MAOI-induced hypotension and results in a NORMALIZATION of blood pressure (possibly due to compensating for increased levels of octopamine). Best used under the supervision of a physician and with access to an emergency antihypertensive (phentolamine, nifedipine, clonidine, chlorpromazine). **DO NOT USE DEXTROMETHORPHAN WITH IRREVERSIBLE, NON-SELECTIVE MAOIs**. DO NOT COMBINE WITH SELEGILINE (4). Tranylcypromine significantly riskier for this use as it has intrinsic sympathomimetic properties and sympathomimetic/monoamine uptake blocking metabolites.
(7) Precursor loading (l-phenylalanine, l-tyrosine): highly individualized dosage. Vastly
more effective if combined with selegiline (or other MAOIs). Remote possibility of untoward effects with irreversible inhibitors of MAO-A. Excessive dosages combined with selegiline may result in agitation, [hypo]mania, etc. See pubmed for articles on combining these with selegiline.
DO NOT USE L-DOPA IN THIS CASE WITHOUT PROFESSIONAL GUIDANCE AS IT HAS MANY POTENTIAL UNTOWARD EFFECTS, AND SYNTHESIS OF DOPAMINE FROM L-DOPA IS NOT RATE-LIMITED.(8) CATECHOLAMINE/MONOAMINE UPTAKE BLOCKERS (methylphenidate, bupropion, sibutramine, atomoxetine, venlafaxine, nomifensine, amineptine, medifoxamine, minaprine, cocaine (buccal or oral only!), desipramine, reboxetine etc. Increases intrasynaptic concentrations of catecholamines via uptake blockade instead of collapsing uptake transporter proton gradient/reverse diffusion. May prevent some forms of neurotoxicity (only a concern if you are overheating, using doses that are too high, or possibly using methamphetamine). Methylphendiate has been shown in particular to have beneficial effects in animal studies. Use modestly to avoid untoward potentiation of
psychostimulant effect. Atomoxetine is a kappa opioid agonist and I refuse to recommend it given other superior agents. May require reduced dose of d-amphetamine. CONCOMITANT USE OF THESE WITH ANY OTHER AGENTS ABOVE BESIDES MG/ZN IS POTENTIALLY DANGEROUS.(9) Modest (25-75mg qd-tid) doses of caffeine: Adenosine 2A receptor antagonism attenuates amphetamine tolerance. cAMP PDE inhibitory effects (I think). Increases NE release.
Watch for hypertension. Diuretic effect may lower d-amphetamine plasma levels via increased renal clearance. Use caution if you do this all the time (cardiovascular, psychiatric, other medical issues)! Coffee contains MAO inhibitors (beta-carboline type).(10) Alkaline substances (baking soda, calcium carbonate antacids, etc.): Slows renal elimination , increases plasma levels/duration of action. 1-2g calcium carbonate every 4h as needed is a possible dose. Baking soda is sodium bicarbonate; too much salt! Avoid habitual use as many untoward effects will occur.
(11) Drugs that regulate Ca++ influx: nefiracetam (demonstrated for opioid tolerance in animals), possibly nimodipine, verapimil, lamotrigine, etc. D-amphetamine increases Ca++ influx, theoretically resulting in tolerance. These agents could prevent that. NOTE: agents in (1), especially memantine, do this via a different mechanism. Many of these agents may negate the beneficial effects of d-amphetamine. Nefiracetam is a potent nootropic.
(12) Kava Kava extract: MAO-B inhibition, NE uptake blockade, Ca++ blocking effects.
(13) Cigarettes/nicotine/nicotinic drugs: Contains beta-carboline MAO-A inhibitors. The smoke also inhibits MAO-B (50% in most smokers I think). Nicotinic effect increases DA release/attention. Galantamine is better than donapezil, rivastigmine for this purpose IMHO. Abbott labs is testing a nicotinic agonist for ADHD. Contraindications/warnings too obvious to detail.
(14): Low-dose amisulpride/sulpiride: Preferential D2 autoreceptor antagonists. Increase DA release and prevent desensitization of autoreceptors which will normally lead to negative feedback-based inhibition. At high doses of d-amphetamine this is unnecessary, but the goal is to keep the dose low, right? Many possible untoward effects; sometimes no effect at all.
(15) Aspirin? Others I am too tired of writing to mention/recall or am not familiar with ... ?
Most robust combinations could be: (1),(3),(6) or (1),(3),(5), or possibly (1),(3),(4),(5), all with or without (7) or (8).
I am not a doctor; the veracity of this information is intended but not guaranteed. You might do serious harm to yourself employing these agents without the guidance of a physician/psychopharmacologist.
poster:Chairman_MAO
thread:616906
URL: http://www.dr-bob.org/babble/20060304/msgs/616992.html