Tetradotoxin-potrebno vise informacija

[Klemovanje]

POzzz od kolege sa ekonomskog faxa , poshtovanje za rad i predanost na ovom foumu za sve moderatore i admine. Ovim putem bih
zeleo da pokrenem jednu veoma zanimljivu temu u vezi farmakologije . Naime uskoro pochinje distribucija leak buducnosti za hemoterapiju i odvikavanje od droge ( raznih vrasta) , to je najveci uspesh kineske farmakologije , rech je o TTX-u , tetrodotoxin-u , supstanci zivotinjskog porekla iz japanske puffer ribe koja zauzima posebno mesto u ishrani japanaca , kineska farmakoloshka kompanija
pokrenula ja proizvodnju lekova na bazi ove supstance , inache ova supstanca je otrovnija preko 2.800 puta od cijanida i  preko 10.000 puta ima jache anestetsko dejstvo od kokaina , ko zna neshto o ovome neka pisheee please. Zanimljiv site je . www.global-bio.com ,A jedna kompanija iz srbije je trenutno zastupnik za evropu i afriku , zato molim za malo podrshke u tome . Unapred zahvalan

[Vampire 666]

Hmm, uvek su mi ta chuda bla sumnjiva. Moracu da se raspitam....

[mullala]

Ja ne znam nista strucno o tetrodotoxinu (to cu probati da saznam u skorije vreme), ali znam da se ta riba jede  u japanu, i boljim japanskim restoranima po svetu, spremljena na poseban nacin kako bi se eliminisao toxin. Kuvari se specijalno obucavaju u te svrhe, a onaj ko jede je za prvih par zalogaja preseljen u posebnu sobicu (samicu) da ostali gosti ne bi morali da gledaju kako covek umire za nekoliko sekundi u slucaju da je riba lose spremljena.
O toj ribi se radi, jel tako?
A sad odoh da trazim o tetradotoxinu

EDIT: Pih, i nije taaako strasno: "Death usually occurs within 4 to 6 hours, with a known range of about 20 minutes to 8 hours."

EDIT2: In living animals the toxin acts primarily on myelinated (sheathed) peripheral nerves and does not appear to cross the blood-brain barrier. 
Izaziva paralizu blokadom Na kanala, sto rade i neki njemu srodni toxini (koji su cak i jaci od njega). Obzirom da sadrzi guanidino grupu, i da je pri fizioloskom pH u jonizovanom stanju, nikako ne moze ni da prodje krvno mozdanu barijeru (koja je lipofilna), pa zato deluje na periferne nerve. Intoxikacija zapocinje neosetljivoscu i trnjenjem usta i jezika pa onda progresivno dalje... Neosetljivost ostalih delova koze sluzokoze, pa bolovi... Pa onda pocinje paraliza misica (zbog nemogucnosti prenosenja signala sa nerava). Umire se od prestanka disanja uz potpuno ocuvanu svest do samog kraja... Uzas ...

Mala digresija: Pogledajte Nightmares and Dreamscapes, epizoda Autopsy Room Four, radjeno po romanu Stevena Kinga, na tu temu

A sada trazim dalje...

EDIT3: Yupac naziv: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano-10aH-[1,3] dioxocino[6,5-d]pyrimidine-4,7,10,11,12-pentol
Struktura: http://www.cfsan.fda.gov/~mow/tet.html

Inace, taj toxin proizvode bakterije, ane riba (ili neka druga zivotinja) u kojoj se nalazi. A ribica je uspela obicnom tackastom mutacijom gena za Na kanal da postane imuna na toxin, tj da spreci njegovo vezivanje za isti...

Interesantno da nema bas mnogo podataka (tacnije nisam jos uvek ni na sta naisla, i cudi me da ne pise nista na wikipediji) o koriscenju tetradotoxina u svrhe hemoterapije i odvikavanja od droge. Ne znam ni na osnovu koje njegove farmakoloske osobine bi to bilo izvodljivo, ali trazim dalje

EDIT4: "Because of its potency -- it is 1250 times deadlier than cyanide -- the toxin is an important tool in modern neurological research. In diluted form it is also used as a painkiller for victims of neuralgia, arthritis and rheumatism."

Aleluja:

Tetrodin™

A revolutionary non-narcotic pharmaceutical, with potent analgesic properties. With experiments to date Tetrodin™ has shown to provide a safe, cost effective primary withdrawal treatment solution for heroin and other opiate addiction to substances such as morphine, opium and methadone.  These highly addictive drugs work by sending an active ingredient to the opioid receptors of the brain, creating an euphoric feeling. Addicted users experience a continued physical craving for the euphoric results produced by repeated use, exacerbated by the fear of the withdrawal symptoms that, in all cases, follows discontinued use of the drug.  These symptoms generally include severe pain, sweating, vomiting and tremors.

The Company believes that treatment with Tetrodin™ can effectively reduce or eliminate the pain and other symptoms associated with withdrawal while the body eliminates the opiate residue to the point where it is no longer detectable in the bloodstream. Tetrodin™ has shown to date to have no addictive properties.

WEX recently completed a Phase IIa study.  The results suggested that the use of a four-day pre-treatment regimen of 30 μg of subcutaneous tetrodotoxin (Tetrodin™), two times a day, prior to the initiation of withdrawal symptoms with naloxone, does not alleviate the withdrawal symptoms, as assessed in 14 methadone-maintained subjects.  However, the results are not conclusive since the study included a relatively small number of subjects with a large variation in response, a small carryover effect was observed from one treatment period to the next and tetrodotoxin was not administered while subjects were experiencing withdrawal symptoms with this pre-treatment study design.

A significant finding from this study was that the safety profile of tetrodotoxin was similar to that observed in previous studies and the administration of naloxone following tetrodotoxin versus placebo treatment did not produce different safety profiles.

Most importantly, the experience with this study has helped the Company to better understanding tetrodotoxin’s mechanism of action, such that tetrodotoxin treatment may only be effective when administered during the withdrawal period.   Hence, it is possible that in a larger study with a different treatment regimen, tetrodotoxin may prove to have clinical efficacy in this indication.
The Company will continue to focus its efforts on the commercialization of Tectin™ for pain management and therefore, will not pursue the development of Tetrodin™ in Canada until further resources are available through a partnership/collaboration.

U pitanju je kompanija WEX pharmaceuticals.
Preuzeto sa: http://www.wextech.ca/products/tetrodin.htm

EDIT5: necu vise valjda...

HIV-1-associated cognitive/motor complex is a frequent neurological complication of the acquired immunodeficiency syndrome (AIDS). The pathogenesis of this syndrome implicates immunopathological and toxic events such as the production of cytokines. The HIV envelope glycoprotein gp120 seems also to play a major role in this process. Gp120 could produce a slow neuronal death probably via the release of neurotoxic factors by CNS macrophages/monocytes. NMDA antagonists and Ca2+ channel blockers in vitro have a powerful neuroprotective effect against gp120 neurotoxicity. The purpose of the present work is to determine whether gp120-induced neurotoxicity is associated with an abnormal neuronal depolarization induced by putative neurotoxins. We have compared in vitro the neuroprotective effects of Tetrodotoxin a Na+ channel blocker, the Ca2+ channel blocker nifedipine and the NMDA antagonist MK-801 in primary cortical neurons taken from embryonic rat and intoxicated with gp120. We observed comparable neuroprotective effects with the 3 precited compounds suggesting that gp120-induced neurotoxic factors act on Na+ channels, NMDA receptors and Ca2+ channels in a cascade of cellular events. We confirmed that the presence of macrophages is needed to trigger a marked gp120-induced neurotoxicity. These results underline the fact that depolarization is an important component of gp120 neurotoxicity in primary neuronal cultures.

Preuzeto sa: http://www.aidshivresearch.com/showabstract.php?pmid=8015723

Ok, odjavljujem se
Pozzz...