Hive General Discourse

	Main Index Search Register Login Who's Online FAQ Links
	Main Index Search Register Login Who's Online FAQ Links

	3 Online, 0 Active		You are not logged in

This is a historical archiveThe forum is read-only. Private information has been removed. It is not possible to login.

	General Discourse

All 5 posts Subject: Reactions of the Neurotoxin Tryptamine-4,5-dione Please login to post Down

jsorex
(Hive Addict)
03-18-04 21:27
No 495998
User Picture       Reactions of the Neurotoxin Tryptamine-4,5-dione

Check this out:
Chem. Res. Toxicol., 17 (3), 357 -369, 2004DOI:10.1021/tx020084k

Reactions of the Putative Neurotoxin Tryptamine-4,5-dione with L-Cysteine and Other Thiols

Xiang-Rong Jiang, Monika Z. Wrona, Susan S. Alguindigue, and Glenn Dryhurst
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019

Received September 16, 2002

Abstract:

Tryptamine-4,5-dione (1) is formed by oxidation of 5-hydroxytryptamine by reactive oxygen and reactive nitrogen species. Dione 1 is a powerful electrophile that can covalently modify cysteinyl residues of proteins and deactivate key enzymes. Thus, 1 has been suggested to play a role in the degeneration of serotonergic neurons in brain disorders such as Alzheimer's disease or evoked by amphetamine drugs. However, if formed in the brain, it is also likely that 1 would react with low molecular weight thiols such as cysteine (CySH) and glutathione (GSH). The resulting metabolites might not only contribute to the degeneration of serotonergic neurons but also, perhaps, serve as biomarkers of such neurodegeneration. In this investigation, it is shown that in oxygenated buffer at pH 7.4 dione 1 reacts with CySH and other low molecular weight sulfhydryls such as GSH, N-acetylcysteine, and cysteamine to form, first, the corresponding 7-S-thioethers of the dione. However, unlike the glutathionyl and N-acetylcysteinyl conjugates of 1, the 7-S-cysteinyl conjugate is very unstable at pH 7.4 forming a number of novel products, the nature of which are dependent on the relative concentrations of 1 and CySH. These products have been isolated, and spectroscopic and other evidence is provided in support of their proposed chemical structures.

3

Vitus_Verdegast
(Hive Addict)
03-20-04 13:33
No 496309
User Picture       what amphetamine drugs?

That description on itself says absolutely nothing. What compounds are they talking about? There are a phletoria of analogs known, and each compound has its specific characteristics.

p-Chloroamphetamine and p-iodoamphetamine are indeed potent serotonergic neurotoxins.

2,4-Dihydroxyamphetamine, to name one, is also an amphetamine drug but its phenolic groups render it insufficiently lipophilic to effectively pass the blood brain barrier. How can it be a neurotoxin then? wink

http://www.movieconnection.it/schede/nosferatu.jpg

Rhodium
(Chief Bee)
03-20-04 15:53
No 496332
User Picture       intracerebral

2,4-Dihydroxyamphetamine, to name one, is also an amphetamine drug but its phenolic groups render it insufficiently lipophilic to effectively pass the blood brain barrier. How can it be a neurotoxin then?

It may be neurotoxic upon intracerebral injection... wink

^{The Hive - Clandestine Chemists Without Borders}

jsorex
(Hive Addict)
03-21-04 18:10
No 496475
User Picture       Of course they mean the more comonly abused...

Of course they mean the more comonly abused amphetmines that are clinically relevant. Anyway it says here Post 461700 (jsorex: "Toxicology", General Discourse) that:

Changes in mood, excitation, motor movements, sensory perception, and appetite appear to be mediated more directly by central dopaminergic alterations. It has been postulated that serotonin alterations contribute to the amphetamine-related mood changes, psychotic behavior, and aggressiveness.

But again they give no refs for this

3

indole_amine
(Stranger)
09-17-04 17:48
No 531821
      tryptamine-4,5-dione related to amph toxicity?

laugh look what I just found... laugh

A Putative Metabolite of Serotonin, Tryptamine-4,5-Dione, Is an Irreversible Inhibitor of Tryptophan Hydroxylase: Possible Relevance to the Serotonergic Neurotoxicity of Methamphetamine

(Monika Z. Wrona and Glenn Dryhurst; Chem. Res. Toxicol. 2001, 14 (9) (1184 -1192))
DOI:10.1021/tx010037c

Abstract
Tryptamine-4,5-dione (T-4,5-D) is formed as a result of oxidation of 5-hydroxytryptamine by superoxide (O2-·), nitric oxide (NO·), and peroxynitrite (ONOO-). T-4,5-D rapidly inactivates tryptophan hydroxylase (TPH), derived from rat brain, probably as a result of covalent modification of active site cysteine residues. The activity of TPH exposed to T-4,5-D cannot be restored by anaerobic reduction with dithiothreitol (DTT) and ferrous iron (Fe2+) indicating that the inactivation is irreversible. 7-S-Glutathionyl-tryptamine-4,5-dione, formed by the rapid reaction between T-4,5-D and glutathione, also inhibits TPH but in this case the activity is restored by anaerobic reduction with DTT/Fe2+. The results of this investigation may be relevant to the initial reversible and subsequent irreversible inactivation of TPH evoked by methamphetamine and 3,4-methylenedioxymethamphetamine.

About neurotoxic amphetamine metabolites: they specifically mean methamphetamine and 3,4 substituted compounds when talking about neurotoxicity - at least in this article.. wink

_{indole_amine}

	https://the-hive.archive.erowid.org	the-hive@erowid.org



Powered by Tea & Milk V. 1.7.4, © 2022, the Chimp Computer Services International
Links Erowid Rhodium

	All 5 posts		Subject: Reactions of the Neurotoxin Tryptamine-4,5-dione		Please login to post		Down


		jsorex (Hive Addict) 03-18-04 21:27 No 495998				Reactions of the Neurotoxin Tryptamine-4,5-dione
						Check this out: Chem. Res. Toxicol., 17 (3), 357 -369, 2004DOI:10.1021/tx020084k Reactions of the Putative Neurotoxin Tryptamine-4,5-dione with L-Cysteine and Other Thiols Xiang-Rong Jiang, Monika Z. Wrona, Susan S. Alguindigue, and Glenn Dryhurst Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019 Received September 16, 2002 Abstract: Tryptamine-4,5-dione (1) is formed by oxidation of 5-hydroxytryptamine by reactive oxygen and reactive nitrogen species. Dione 1 is a powerful electrophile that can covalently modify cysteinyl residues of proteins and deactivate key enzymes. Thus, 1 has been suggested to play a role in the degeneration of serotonergic neurons in brain disorders such as Alzheimer's disease or evoked by amphetamine drugs. However, if formed in the brain, it is also likely that 1 would react with low molecular weight thiols such as cysteine (CySH) and glutathione (GSH). The resulting metabolites might not only contribute to the degeneration of serotonergic neurons but also, perhaps, serve as biomarkers of such neurodegeneration. In this investigation, it is shown that in oxygenated buffer at pH 7.4 dione 1 reacts with CySH and other low molecular weight sulfhydryls such as GSH, N-acetylcysteine, and cysteamine to form, first, the corresponding 7-S-thioethers of the dione. However, unlike the glutathionyl and N-acetylcysteinyl conjugates of 1, the 7-S-cysteinyl conjugate is very unstable at pH 7.4 forming a number of novel products, the nature of which are dependent on the relative concentrations of 1 and CySH. These products have been isolated, and spectroscopic and other evidence is provided in support of their proposed chemical structures. 3



		Vitus_Verdegast (Hive Addict) 03-20-04 13:33 No 496309				what amphetamine drugs?
						That description on itself says absolutely nothing. What compounds are they talking about? There are a phletoria of analogs known, and each compound has its specific characteristics. p-Chloroamphetamine and p-iodoamphetamine are indeed potent serotonergic neurotoxins. 2,4-Dihydroxyamphetamine, to name one, is also an amphetamine drug but its phenolic groups render it insufficiently lipophilic to effectively pass the blood brain barrier. How can it be a neurotoxin then? http://www.movieconnection.it/schede/nosferatu.jpg



		Rhodium (Chief Bee) 03-20-04 15:53 No 496332				intracerebral
						2,4-Dihydroxyamphetamine, to name one, is also an amphetamine drug but its phenolic groups render it insufficiently lipophilic to effectively pass the blood brain barrier. How can it be a neurotoxin then? It may be neurotoxic upon intracerebral injection... ^{The Hive - Clandestine Chemists Without Borders}



		jsorex (Hive Addict) 03-21-04 18:10 No 496475				Of course they mean the more comonly abused...
						Of course they mean the more comonly abused amphetmines that are clinically relevant. Anyway it says here Post 461700 (jsorex: "Toxicology", General Discourse) that: Changes in mood, excitation, motor movements, sensory perception, and appetite appear to be mediated more directly by central dopaminergic alterations. It has been postulated that serotonin alterations contribute to the amphetamine-related mood changes, psychotic behavior, and aggressiveness. But again they give no refs for this 3



		indole_amine (Stranger) 09-17-04 17:48 No 531821				tryptamine-4,5-dione related to amph toxicity?
						look what I just found... A Putative Metabolite of Serotonin, Tryptamine-4,5-Dione, Is an Irreversible Inhibitor of Tryptophan Hydroxylase: Possible Relevance to the Serotonergic Neurotoxicity of Methamphetamine (Monika Z. Wrona and Glenn Dryhurst; Chem. Res. Toxicol. 2001, 14 (9) (1184 -1192)) DOI:10.1021/tx010037c Abstract Tryptamine-4,5-dione (T-4,5-D) is formed as a result of oxidation of 5-hydroxytryptamine by superoxide (O2-·), nitric oxide (NO·), and peroxynitrite (ONOO-). T-4,5-D rapidly inactivates tryptophan hydroxylase (TPH), derived from rat brain, probably as a result of covalent modification of active site cysteine residues. The activity of TPH exposed to T-4,5-D cannot be restored by anaerobic reduction with dithiothreitol (DTT) and ferrous iron (Fe2+) indicating that the inactivation is irreversible. 7-S-Glutathionyl-tryptamine-4,5-dione, formed by the rapid reaction between T-4,5-D and glutathione, also inhibits TPH but in this case the activity is restored by anaerobic reduction with DTT/Fe2+. The results of this investigation may be relevant to the initial reversible and subsequent irreversible inactivation of TPH evoked by methamphetamine and 3,4-methylenedioxymethamphetamine. About neurotoxic amphetamine metabolites: they specifically mean methamphetamine and 3,4 substituted compounds when talking about neurotoxicity - at least in this article.. _{indole_amine}

All 5 posts	End of thread	Top