Talk:MPTP

Authenticate Statement

Under the heading Synthesis and Uses the following statement was made:

"In one test of the substance, two of six human subjects died."

This sounds as if patients were experimentally treated with MPTP. Is this correct? The citation is to a book I would need to get through inter-library loan. I have a feeling this is referring to the incident in 1980s where a bad batch of synthetic heroin turned up on the streets of Silicon Valley. The junk was tainted with MPTP. Once injected, it damaged the substantia nigra, reducing the drug user to a catatonic state.

This sounds suspiciously like a paraphrased quote from the NOVA special on MPTP and Parkinson's Disease called "The Case of the Frozen Addict" (originally broadcast on 02/18/86). The NOVA special talks about chemist Dr. Albert Ziering who was working at Hoffman-La Roche in the 1940's, and related that MPTP was experimented with (by Hoffman-La Roche chemists) as a Parkinson's treatment in the 1950's. The MPTP was given to rats with no effects, then to six monkeys at high doses yielding tardive dyskinesia like effects then death; finally MPTP was given to six humans, two of which died. --74.179.120.107 (talk) 22:51, 25 November 2010 (UTC)

Structure

The structure given for MPTP is NOT correct. There is a doubble bond in the tetrahydropyrridin ring. This unsatuaration should be omitted. Please redraw the structure. Ake Bergman Professor in Environmental Chemistry Stockholm University (email removed to prevent spam) —Preceding unsigned comment added by 92.32.86.223 (talk) 06:48, 7 September 2008 (UTC)

If that ring were fully saturated, why would it be named tetrahydro…? The structure given in both Pubchem and ESIS have the unsaturation in their diagram. Pubchem and MeSH search both describe the compound of this name as having the biochemical properties listed in the Wikipedia article here. Do you have some cites to support an alternate structure? DMacks (talk) 07:04, 7 September 2008 (UTC)

What discovery in users of illicit drugs?

I think the title of this section is misleading. The title suggests that MPTP toxicity was the product of illicit drug use. In Barry Kidston, he was poisoned by MPTP because he injected himself with the compound, not because of his cocaine use. The seven cases in Santa Clara were also the result of injecting or ingesting something similar (MPPP), not because of the use of illicit drugs (of which none of were named in this article).

R. Robinson, 21 October 2008 —Preceding unsigned comment added by 75.71.207.72 (talk) 06:03, 21 October 2008 (UTC)

Using MPPP recreationally would be illicit drug use.

Structural Drawing vs IPUAC Name

Dear Madams and Sirs:

Your article on MPTP states that the IUPAC name for that substance is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Would you please check to see whether that stated name is correct?

According to the stated name, nitrogen occupies the "1" position in the heterocyclic ring, since the nitrogen in the structural formula is the atom to which the methyl group is bound. However, while the structural formula shows no hydrogen bound to that nitrogen, the stated name indicates that a hydrogen is bound to that nitrogen. It is hard to see how the stated name and the structural formula can both be correct.
Sincerely yours,

James W. Frederiksen, MD
Northwestern University Feinberg School of Medicine
Chicago, IL 60611
[excessive personal info removed -- DMacks]

To learn more about the Bluhm Cardiovascular Institute, please visit our web site at http://www.nmff.org/clinicaldepts/department.asp?id=66!"
—The preceding unsigned comment was added by James W. Frederiksen (talk • contribs) 14:38, 31 May 2006 (UTC)

The IUPAC web site verifies the name, so the graphic must be wrong. I have found some images of MPTP on Google image search that match my graphic…

• http://www.neurosci.pharm.utoledo.edu/MBC3320/dopamine.htm
• http://www.chemsoc.org/chembytes/ezine/1997/stachuls.htm
• http://holivo.pharmacy.uiowa.edu/morphine/chsix/mptp.html

…and some that don't.

• http://pharma1.med.osaka-u.ac.jp/textbook/Antiparkinsonian/Antiparkinsonian.html
• http://www.parkinson-web.de/popup/ursach_mptp1.html
• http://connection.lww.com/products/foye/quizch20.asp

Can anyone familiar with chemistry figure this out?

Foobaz·o< 01:49, 19 September 2006 (UTC)

If the image is correct, I think the name should be 1-methyl 4-phenyl 2,3,6-trihydropyridine. If the name is correct, the structure should have a hydrogen on the nitrogen atom, as Dr. Frederiksen describes. So now we just have to find which is correct.

This page: [1] shows MPTP as it is in the article's image, and has a reference to Chem.Eng.News 1981, 71, which I don't have access to. If someone who does have access could look at that, it might be helpful. Gary 03:10, 19 September 2006 (UTC)

The Aldrich catalog gives the name as "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine" and the image as drawn in the article (double bond in conjugation with the phenyl).[2]. "Hydro" doesn't literally mean "an extra hydrogen atom is present", just that there is not an expected double bond present. Consider the parent pyridine structure, with double bonds between N (position 1, using the given numbering) and C2, between C3 and C4, and between C5 and C6. If you undo the double bonds on positions 1,2,3,6, you get the image as given. Adding three hydrogens wouldn't even give a stable structure, since you would not have acquired the lone-pair on N. OTOH, even if we take the name as a literal instruction to hydrogenate the N1-C2 and C3-C6 double bonds, you get the same structure as drawn except with the N protonated (for example, the known MPTP•HCl salt). So the image as drawn is just the conjugate base of that salt. Foobaz: I disagree with your image-search results—the osaka-u and the lww sites both have the image as drawn in the wikipedia. DMacks 05:29, 19 September 2006 (UTC)

See Wikipedia:Reference_desk/Science#MPTP_article_image for more discussion on the image's correctness. Foobaz·o< 01:54, 20 September 2006 (UTC)

I believe DMacks is correct. Here [3] is the IUPAC guide for naming these, although this specific case isn't covered, where the double bond is removed a methyl group (instead of another hydrogen) is attached to the nitrogen. It does say that "hydro" is added in pairs, so "trihydropyridine" is probably out. The images and descriptions found can't be all wrong, can they? Bennybp 03:20, 20 September 2006 (UTC)

Rats

The neurotoxicity of MPTP was discovered in 1976 after Barry Kidston, a 23-year-old chemistry graduate student in Maryland, synthesized MPPP incorrectly and injected the result. It was contaminated with MPTP, and within three days he began exhibiting symptoms of Parkinson's disease. The National Institute of Mental Health found traces of MPTP in his lab and eventually discovered its effects by testing the chemical on rats."

According to my university lectures, rats are immune to the neurotoxic effects of MPTP. This means its is unlikely these effects were confirmed by testing on rats as stated in the article.

Barry Kidston's attempt at making MPPP resulted in MPTP via sloppy chemistry. MPTP had actually been discovered as far back as 1947 (first published account) by Albert Ziering. MPPP, true enough, does have effects on rats, however the paralyzing like effects wear off quickly, that is these effects do not last in rats. MPTP does NOT affect rats. MPTP does affect monkeys and humans, and is "reversible" with levadopa. --74.179.120.107 (talk) 23:00, 25 November 2010 (UTC)

Apes?

Are you sure it was initally tested on apes? The article later says it was first tested in squirrel monkeys (which aren't apes).

Langston's patients

Didn't Langston have six patients, not seven as stated? They were Connie, George, Juanita, David, Bill and Toby. If there is a seventh patient who was it? —The preceding unsigned comment was added by 134.153.182.147 (talk • contribs) 18:08, 26 February 2007 (UTC)

This article reads a bit Langston-centric. Richard8081 20:39, 12 September 2007 (UTC)

"MPP+ interferes with complex I of the electron transport chain, a component of mitochondrial metabolism, which leads to cell death and causes the buildup of free radicals, toxic molecules that contribute further to cell destruction." Is there any in vivo demonstration that inhibition of electron flow at Complex I leads to cell death; that inhibition of electron flow at complex I causes the buildup of free radicals; or that, in vivo now, toxic free radicals contribute to cell destruction? In vivo, okay? Not in a cell free system, although that is how we discover things; is there any demonstration that any of this actually takes place? Richard8081 (talk) 05:01, 17 July 2012 (UTC)

Stem Cells

Editing the statement about stem cells. These "stem cells" were actually fetal tissue grafts, not embryonic stem cells. Embryonic stem cells are pluripotent cells taken from the inner cell mass of a blastocyst. These cells were partially differentiated multipotent cells taken from fetuses. The stem cells in question are technically what is colloquially referred to as "adult" stem cells.Jkhamlin (talk) 05:06, 3 May 2009 (UTC)

References

Reference 6 describes only the corresponding 2-arylpiperidines, not the 4-arylpiperidines (and thus not MPTP).

Reference 7 probably should refer to volume 65 of that series. In volume 64 (also from 1994) there is a discussion of mercury intoxication on page 369. Have no access to the original volume 65 to check it, though. — Preceding unsigned comment added by 138.246.2.48 (talk) 10:46, 10 October 2011 (UTC)

Dangerously unclear statements

The introduction contains this statement:

"While MPTP itself has no psychoactive effects, the compound may be accidentally produced during the manufacture of MPPP, a synthetic opioid drug with effects similar to those of morphine and pethidine (meperidine).'"

And the next section, Toxicity, starts with this passage:

"Injection of MPTP causes rapid onset of Parkinsonism, hence users of MPPP contaminated with MPTP will develop these symptoms. MPTP itself is not toxic, and as a lipophilic compound can cross the blood–brain barrier."

In regard to a substance, the word psychoactive means causing mental effects. it doesn't matter how this happens in the body, such as whether the substance has turned into another substance first, and that one more directly has the mental effects. The original substance is still psychoactive.

Same principle is true for the word toxic.

So it an extremely dangerous mistake to claim "MPTP is not toxic".

To a biochemist, to be sure, just how MPTP is toxic is important to know, and of course the information that MPTP first becomes MPP+, and then this chemical does the direct damage, should be included somewhere in the article.

But it is a very, very bad idea to claim that "MPTP itself is not toxic", because 99.99% of all people will misinterpret that to mean that it is safe to put in the human body. And it certainly is not safe to put in the human body.Daqu (talk) 16:18, 2 November 2014 (UTC)

External links modified

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Alternate name?

Is this compound also called MTPT? Because it seems to be called that in multiple articles. 204.11.186.190 (talk) 17:48, 4 November 2022 (UTC)

"Prodrug"

The metabolite MPP+ is a neurotoxin with no therapeutic value. It is not a drug. Therefore, MPTP is not a prodrug. Grassynoel (talk) 01:51, 10 March 2023 (UTC)