BPAP - Monoamine activity enhancer

[QUARE]

Benzofuranylpropylaminopentane (BPAP) is a monoamine activity enhancer. From what I read on wiki : unlike stimulant drugs like amphetamine, which release a flood of these neurotransmitters in an uncontrolled manner, BPAP instead only increases the amount of neurotransmitter that gets released when a neuron is stimulated by receiving an impulse from a neighbouring neuron.

Is that kind of chemical used medicaly ? Does anyone have try something similar to that ?

 

[sekio]

It's been talked about before, there are rumblings that it may be toxic to the liver though - as other benzofurans are.

The phenyl analogue, PPAP, is known too. but doesn't seem to have been used in humans.

 

[QUARE]

So you suggest that PPAP is probably less toxic because the furan ring as been removed ?

What kind of effect would those chemical do ? I imagine that is cause stronger excitement when, exemple; you get good news, receive a gift, win a price or do an activity you enjoy.

 

[knockout_mice]

It is supposedly hard to synthesize and unstable (degrades pretty quckly), that's why it didn't hit the nootropic market yet. If anyone knows about stable analogs, tell us please!

(or move this thread into neuroscience and pharmacology discussion...)

 

[sekio]

od --> nspd

 

[QUARE]

How quickly does it degrade ? Those drugs look so nice its like mind enhancing without the side effect. Well thats how It look like to me.

 

[immad]

Benzofuranylpropylaminopentane (BPAP) is a monoamine activity enhancer. From what I read on wiki : unlike stimulant drugs like amphetamine, which release a flood of these neurotransmitters in an uncontrolled manner, BPAP instead only increases the amount of neurotransmitter that gets released when a neuron is stimulated by receiving an impulse from a neighbouring neuron.

Is that kind of chemical used medicaly ? Does anyone have try something similar to that ?

This does sound like reuptake inhibition instead of mono-amine release, only increasing the already ongoing activity. How does this work?

 

[QUARE]

Rather than a reuptake inhibitor, reuptake is still possible because it has no effect on transporter. It release more monoamine in the synapse but rather then releasing all the monoamine at once like amphetamine would do, it would be done with a relative control.

 

[endotropic]

Any guesses for a molecular mechanism? VMAT selective inhibitor? Any known protein affinities?

 

[knockout_mice]

http://morelife.org/references/full_papers/14659999.pdf

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] is a catecholaminergic and serotonergic activity enhancer that increases impulse-evoked catecholamine and serotonin release from nerve terminals, and is a candidate for symptomatic treatment of early Parkinson’s disease. We now report the catecholamine and serotonin transporter-mediated actions of (-)-BPAP. The effects of (-)-BPAP on inhibition of neurotransmitter uptake and radioligand binding were assessed using human embryonic kidney 293 cells (HEK 293 cells) expressing cDNA for the human dopamine transporter (hDAT), norepinephrine transporter (hNET), and serotonin transporter (hSERT). The IC 50 values for the effects of (-)-BPAP on [ 3 H]dopamine, [ 3 H]norepinephrine, and [ 3 H]serotonin uptake were 42(+-)9, 52(+-)19, and 640(+-)120 nM, respectively. The IC 50 values for the effects of (À)-BPAP on [ 125 I]3h-(4-iodophenyl)tropane-2h-carboxylic acid methyl ester ([ 125 I]RTI-55) binding to hDAT, hNET, and hSERT were 16(+-)2, 211(+-)61, and 638(+-)63 nM, respectively. The effects of (-)-BPAP on spontaneous and tyramine-induced norepinephrine and dopamine release from rat brain synaptosomes using a superfusion system were also assessed.

Tyramine but not (-)-BPAP potentiated norepinephrine release. Furthermore, (-)-BPAP inhibited tyramine-induced norepinephrine release. Thus, (-)-BPAP may block tyramine-induced adverse effects such as hypertensive crisis. The actions of (-)-BPAP on the spontaneous and tyramine-induced dopamine release resembled its effects on norepinephrine release. We conclude that (-)-BPAP is not only catecholaminergic and serotonergic activity enhancer, but also a norepinephrine and dopamine uptake inhibitor and a weak serotonin uptake inhibitor that does not possess a tyramine-like action on catecholamine release, and is an inhibitor of tyramine-induced release of norepinephrine.

The effects of (-)-BPAP on dopamine and norepinephrine
uptake were more potent than those of cocaine, while its
potency at inhibiting serotonin uptake was weaker than that
of cocaine.

CAE/SAEs enhance release of catecholamines and sero-
tonin from the isolated rat brain stem, but not without
electrical stimulation (Knoll et al., 1996, 1999). Thus,
CAE/SAEs behave as a kind of enhancer in amine release
depending on the firing activity of neurons, and can be
distinguished from the catecholamine releasing effects of
tyramine-like compounds and effects of monoamine uptake
inhibitors (Knoll et al., 1996, 1999; Yoneda et al., 2001).
However, as a catecholamine uptake inhibitor is known to
potentiate motor activity (Hemby et al., 1997; Stanford et
al., 2002), the uptake inhibitory effect of (-)-BPAP may be
involved in motor stimulant effects in addition to its CAE/
SAE effect.

 

[endotropic]

I must be confused, because I don't see how this is any different from every other monoamine reuptake inhibitor. Specifically this distinction I'm not getting:

CAE/SAEs enhance release of catecholamines and sero-
tonin from the isolated rat brain stem, but not without
electrical stimulation (Knoll et al., 1996, 1999). Thus,
CAE/SAEs behave as a kind of enhancer in amine release
depending on the firing activity of neurons, and can be
distinguished from the catecholamine releasing effects of
tyramine-like compounds and effects of monoamine uptake
inhibitors (Knoll et al., 1996, 1999; Yoneda et al., 2001).

I'm assuming the isolated rat brain stem has DAT/SERT/NET, so isn't an activity dependent increase in monoamine concentrations consistent with the effects of a reuptake inhibitor?

 

[knockout_mice]

I suppose it's an active "CAE/SAE" in a lower dose which doesn't inhibit DAT/SERT/NET, because its typical dose for reversing cognitive deficits is ~100-200 mcg. It's a weaker SERT inhibitor than cocaine, yet it still elevates serotonin levels in such a low dose. I read Knoll's book about selegiline and BPAP/PPAP, but sadly it's not really specific. I think BPAP mimics the action of endogenous enhancer molecules called trace amines. Maybe it's a TAAR1 agonist... Someone should do a "complete" receptor profile analysis.

 

[immad]

I must be confused, because I don't see how this is any different from every other monoamine reuptake inhibitor. Specifically this distinction I'm not getting:



I'm assuming the isolated rat brain stem has DAT/SERT/NET, so isn't an activity dependent increase in monoamine concentrations consistent with the effects of a reuptake inhibitor?

That was the part I didn't get either.

I suppose it's an active "CAE/SAE" in a lower dose which doesn't inhibit DAT/SERT/NET, because its typical dose for reversing cognitive deficits is ~100-200 mcg. It's a weaker SERT inhibitor than cocaine, yet it still elevates serotonin levels in such a low dose. I read Knoll's book about selegiline and BPAP/PPAP, but sadly it's not really specific. I think BPAP mimics the action of endogenous enhancer molecules called trace amines. Maybe it's a TAAR1 agonist... Someone should do a "complete" receptor profile analysis.

I have to admit not reading the paper, but could it be a strong efficacy with a relatively low affinity reuptake inhibitor?

 

[TheSocialRecluse]

I am aware that this is an old thread, but I just got my hands on some BPAP from what I thought may be a reputable source. Has anyone actually every tried this compound in a solution? If so, does it have a flavor or taste?