is an MDMA / l-deprenyl amalgam possible?

[nanobrain]

in light of the recent MDMA / Parkinsons hullabaloo, a question was asked - can a compound be synthed combining the structures of MDMA and l-deprenyl?

can MDMA's 3,4-methylenedioxy group be tweaked w/the phenethylamine skeleton with deprenyl's n-propargyl group on the other side?

pardon my naivete and fire away with your chastisements and castigations.

 

[phase_dancer]

Not exactly what you asked but rasagiline looks a good candidate.

Mechanism of neuroprotective action of the anti-parkinson drug rasagiline and its derivatives; Silvia Mandel, Orly Weinreb, Tamar Amit, Moussa B.H. Youdim*, Brain Research Reviews 48 (2005) 379– 387

Abstract

The mitochondria are directly involved in cell survival and death. Drugs that protect mitochondria viability and prevent apoptotic cascade mechanisms involved in mitochondrial permeability transition pore (MPTp) will be cytoprotective. Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO) B inhibitor, anti-Parkinson drug.

Unlike selegiline, rasagiline is not derived from amphetamine, is not metabolized to neurotoxic l-methamphetamine derivative, nor does it have sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to L-dopa for patients with early and late Parkinson’s disease (PD), and adverse events do not occur with greater frequency in subjects receiving rasagiline than those on placebo. Controlled studies indicate that it might have a disease-modifying effect in PD that may be related to neuroprotection. Its S-isomer, TVP1022, is a relatively inactive MAO inhibitor. However, both drugs have similar neuroprotective activities in neuronal cell cultures in response to various neurotoxins and in vivo (global ischemia, neurotrauma, head injury, anoxia, etc.), indicating that MAO inhibition is not a pre-requisite for neuroprotection. Structure activity studies have shown that the neuroprotective activity is associated with the propargyl moiety of rasagiline, which protects mitochondrial viability and MPTp by activating Bcl-2 and protein kinase C (PKC), and down regulating pro-apoptotic FAS and Bax. Rasagiline and its derivatives also process amyloid precursor protein (APP) to the neuroprotective-neurotrophic soluble APP alpha (sAPPa) by PKC and MAP kinase-dependent activation of asecretase.

The neuroprotective activity of propargylamine has led us to develop novel bifunctional neuroprotective iron-chelating MAOinhibiting drugs possessing propargyl moiety for the treatment of other neurodegenerative diseases.

RASAGILINE

 

[phase_dancer]

Pharmacological properties of the anti-parkinson drug rasagiline; modification of endogenous brain amine, reserpine reversal, serotonergic and dopaminergic behaviours; John P.M. Finberg and Moussa B.H. Youdim

Neuropharmacology 43 (2002) 1110–1118

Abstract

Rasagiline [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible monoamine oxidase (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson’s disease. In this study we examined effects of rasagiline on CNS monoamine levels, modification of behavioural response to L-tryptophan, fluoxetine and L-DOPA, and reversal of reserpine syndrome. Reserpine-induced ptosis was reversed by rasagiline at doses above 2 mg.kg
1 i.p., which inhibit MAO-A as well as MAO-B, but not at MAO-B-selective doses. However, combination of rasagiline (10 mg.kg
1 i.p.) with L-DOPA or L- tryptophan (50 mg.kg
1 i.p.), or rasagiline (10 mg.kg
1 p.o.) with fluoxetine (10 mg.kg
1 p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and MAO-B by tranylcypromine together with the monoamine precursors.

Following oral administration, levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) were unaffected in hippocampus and striatum after single doses of rasagiline up to 2 mg.kg
1. Following chronic oral administration (21 days, one dose daily), levels of NA, 5-HT and DA in hippocampus and striatum were unaffected by rasagiline at doses up to 1 mg.kg
1. Rasagiline does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit MAO-B but not MAO-A.

 

[phase_dancer]

The starting material could be made various ways. 1,3 benzodioxole condensation with an acid chloride, N protected alanine; or via a nitro intermediate would possibly work.

 

[fastandbulbous]

can a compound be synthed combining the structures of MDMA and l-deprenyl?

Yes, 3,4-methylenedioxy N-methyl-N-propargylamphetamine

Will it have the properties of both of them combined?

Who knows, but N,N-dialkylation of MDMA pretty much abolishes activity, so I wouldn't hold out too much hope

 

[BilZ0r]

As I said to the MAPS article in question:

I'm sure one wouldn't need to go quite that far. Making MDMA an even
more potent and mixed MAO inhibitor would make it quite potent in
regards to its abilities to increase extracellular
dopamine/serotonin/noradrenaline levels, and enzyme inhibition is
always a slightly tricky thing to dose qutie right...

Besides, it's not the amphetamine like effect of MDMA that caused the
increase in forward movement, as it was not mimiced by any other
amphetamine (or SSRI)... so you wouldn't want to noradrenaline
releasing side effects (i.e. cardiovascular) if you didn't need them.

 

[C6H6]

It would be quite easy to make the requested compound by reacting MDMA with propargyl bromide. While it may still have the MAOI properties of deprenyl, it will loos all MDMA-like qualities. Check out MDPL in PiHKAL.

 

[BilZ0r]

Still, a strong serotonergic amphetamine which is a strong MAO-B inhibitor could be made with a less "literal" minded attempt. But as I say, pointless.

 

[jubai]

My own personal experiences with low doses of Deprenyl (1-mg a day) and MDMA showed that while there was a definitive protective effect, the effects of the pills were significantly reduced. I thought it was R-ALA affecting the trip, but a 2nd try with only Deprenyl taught me otherwise.

At 1mg/day I had to take double the quantity of MDMA for the same trip, and even then if felt more 'clean' with less confusion.

 

[Dr. Beat]

My own personal experiences with low doses of Deprenyl (1-mg a day) and MDMA showed that while there was a definitive protective effect, the effects of the pills were significantly reduced. I thought it was R-ALA affecting the trip, but a 2nd try with only Deprenyl taught me otherwise.

At 1mg/day I had to take double the quantity of MDMA for the same trip, and even then if felt more 'clean' with less confusion.

than is exactly my experience:

i only take deprenyl (5 or 10mg) now about 2 hours before taking a pill or two (i never take more than 2 pills), and at no other time.

and i never take deprenyl before or with methamphetamine because it totally takes away the high.