Pharmacology of Halostachine

[neuron]

Pharmacology of Halostachine

Introduction:
Halostachine (N-methylphenylethanolamine) is a very mild sympathomimetic agent with partial adrenergic binding potential (1).

Physiology:
In a study utilizing dogs, intravenous administration of halostachine produced increased pupil diameter, initial tachycardia followed by bradycardia, and an elevated body temperature (2). In another study, oral administration of halostachine produced only mild effects in guinea-pigs and sheep at 100-200mg/kg (3).

Pharmacodynamics:
In an en vitro study of the pharmacodynamics and Structure Activity Relationship (SAR) of various epinephrine-like compounds, halostachine was demonstrated to be 19% as effective as epinephrine in activating the beta2 receptor. As a comparison, synephrine was demonstrated to be 24% as effective. Halostachine was considered to have considerably less ability to activate intracellular cAMP then all other compounds, including synephrine (See picture below)(4).





Pharmacokinetics:
Halostachine is rapidly metabolized by MAO and has a half-life of approximately 5-10 minutes (2, 5).

Structure Activity and Summary:
In comparison to epinephrine, halostachine lacks 2 hydroxyl groups in the m- and p- position on the benzene ring. The absence of these two constituents nearly precludes it from fully activating the adrenergic receptor in its current conformation.

“The presence of the catechol OHs and either the β-OH or the N-CH3 was absolutely required for full activation of the receptor and for full affinity shift. (4)”

Penetration into the CNS will also be limited due to the beta-OH, and due to the absence of an alpha-CH3 (decreased amphipathism). The most likely efficient target for this molecule is the alpha receptor, which is demonstrated above in the study on dogs. Intravenous administration produced mydriasis (alpha1), tachycardia (beta1), elevated body temperature - likely due to excessive vasoconstriction -, and a triggering of the baroreflex. This reflex is activated in response to increased arterial pressure in the absence of beta2 vasodilation. As is clearly demonstrated in the pharmacodynamic study above, halostachine has almost no ability to activate the beta2 receptor and is therefore extremely dissimilar to ephedrine. Since it has almost no capacity to induce cAMP elevation it has no purpose in a fat-loss formula, nor any supplement due to its extremely rapid metabolism. Similarly, since it is a partial-agonist, it will actually decrease adrenergic signaling in the presence of endogenous epinephrine, or exogenous ephedrine.



References:
1) http://med.stanford.edu/kobilkalab/pdf/YaoNCB06.pdf
2) http://www.ncbi.nlm.nih.gov/pubmed/7120117
3) http://www.publish.csiro.au/paper/AR9690071.htm
4) http://molpharm.aspetjournals.org/co...65/5/1181.long
5) http://www.sciencedirect.com/science...b&searchtype=a

[TheWaffleIron]

First!

Edit: Five star thread, will read again.

[Synapsin]

Nice work, but are people using N-methylphenylethanolamine in their products??

Edit: Ah, I see the culprit. Pretty funny, doesn't surprise me in the least.

[neuron]

Nice work, but are people using N-methylphenylethanolamine in their products??

Edit: Ah, I see the culprit. Pretty funny, doesn't surprise me in the least.

Yeah, halostachine is a pretty bunk compound (even worse then synephrine), so I was surprised to see it marketed as the "next ephedrine." It is essentially phenylephrine without the benzene m-OH, so I can't imagine why anyone would think it would have any significant beta-agonism.

[Robboe]

When are you going to cover strychnine as a performance aid?

[Synapsin]

When are you going to cover strychnine as a performance aid?

Is there really an interest in this?

[Bane]

Is there really an interest in this?

It is the world's most ancient used doping agent

[Synapsin]

It is the world's most ancient used doping agent

Yeah, all of the literature I remember for it was super old (and of course you'd know that Mr. Greek ). If nobody has covered it in two weeks, I will, but I'm swamped for the next two weeks.

[Robboe]

Is there really an interest in this?

To use it myself? No chance.

But the idea of a poison being a performance enhancer is fascinating.

[JornT]

Its ironic that I just noticed that Neuron is banned ITT, while this topic is evidence of huge contribution to the board.

[_Smitty_]

Its ironic that I just noticed that Neuron is banned ITT, while this topic is evidence of huge contribution to the board.

sorting through his posts over the last week, i see nothing that would warrant a ban.

[De__eB]

sorting through his posts over the last week, i see nothing that would warrant a ban.

probably a post that got deleted.

It's not all that surprising...hes an incredibly intelligent person, but also kind of vitriolic.

[Bane]

To use it myself? No chance.

But the idea of a poison being a performance enhancer is fascinating.

The dose makes the poison bla bla bla
In middle ages they used it as an appetite enhancer

[Synapsin]

The dose makes the poison bla bla bla
In middle ages they used it as an appetite enhancer

Word. I'll post something tomorrow on Strychnine (Andy already knows what).

[PinchTheBear]

Word. I'll post something tomorrow on Strychnine (Andy already knows what).

Excellent.

[PinchTheBear]

Valuable excerpts from the molecular pharmacology Javitch et. al article cited above:

A comparison of the binding affinities of a series of phenethylamine derivatives for WT revealed a remarkable synergism between the various functional groups present in epinephrine. Binding affinity was essentially unchanged with addition of β-OH, N-CH3, or catechol OHs to phenethylamine. In contrast, when each of these same groups was added to the appropriate compound, already containing the other two groups, to make epinephrine, the increase in affinity was quite large (60- to 120-fold). An initial interaction between two or more contacts may stabilize an intermediate conformation of β2AR, R′, either by altering amino acid side chain rotamer conformations or by a more global conformational change involving the repositioning of transmembrane segments.

Great source. Just wish it didn't come from the elitists of Columbia.

[CanadianChemist]

An oldie but a goodie.

[Synapsin]

Word. I'll post something tomorrow on Strychnine (Andy already knows what).

Sorry, I'll get it up today. Didn't have access to a PC almost all weekend and I forgot I disabled remote access to my work account, hahaha.

[stanfordlee]

Wow,
we are the manufacturer and supplier of Halostachine from China.
This is a new nutritional supplement. this article is really great, I will read it carefully