Serotoniinin takaisinoton estäjä http://en.wikipedia.org/wiki/Serotonin_ ... _inhibitor
κ-opioidi agonisti http://en.wikipedia.org/wiki/Kappa_Opioid_receptor
µ-opioidi agonisti http://en.wikipedia.org/wiki/Mu_Opioid_receptor
Tässä olisi nor-ibogaiini (12-hydroxyibogamine) tietoutta seuraavasta teoksesta:
The Ibogaine Story: Report on the Staten Island Project (1995)
http://ibogaine.mindvox.com/Articles/IbogaineStory/
Tää vaikuttaakin tosi hyvältä ja laajalta teokselta mutta lainaan tässä nyt vain yhdestä kappaleesta
CHAPTER 18: Deborah Mash's Brain
http://ibogaine.mindvox.com/Articles/Ib ... hapter.htm
Mash revealed that Ibogaine blood concentrations reach a low peak from 2 to 4 hrs (during the visualizations), then rapidly fall off--de-methylated by the liver into the longer-acting, water-soluable nor-ibogaine (termed m-1, or metabolite-one)--which peaks more sharply at 4 hrs. and slowly descends during the cognitive evaluation and insomnia phases. Somehow, she indicated, nor-ibogaine may be hanging around the metabolism for some time--perhaps during the several weeks post-treatment when Ibogaine subjects are working off their REM-surplus and don't sleep much. In fact, Mash's team suspects nor-ibogaine is Stanley Glick's elusive, long-acting metabolite--that it was nor-ibogaine which up until 4 months after her first treatment, made Geerte F. "experience colors and light very intensely"--that nor-ibogaine was in fact responsible for the "Ibogaine-aftereffect" which Geerte experienced as "blockading craving until it wore off."
Deborah Mash provided a trove of new details on blood levels and pharmaco-kinetics of Ibogaine and its active metabolite. She identified nor-ibogaine as 12-hydroxy-ibogamine. Miami found the metabolite is active at the mu and delta opiate receptor sites [!], as well as affecting the dopamine and serotonin transporters. Although presumably the same kind "weak" activity seen at the kappa and NMDA receptors, this filled a great deal that was missing when the only thing stopping opiate withdrawal seemed to be some weak kappa receptor activity.
Her slides showed the visualization phase clearly corresponding to a sharp peak in brain levels of the metabolite itself, which may not exit the brain easily and hangs out in there in peak concentrations between 1 and 4 hours.
Dr. Robert Upton presented mathematical analysis of his rat data showing that whereas Ibogaine was converted to metabolite virtually on the first pass through the liver and other organs, systemic clearance of 12-hydroxy-ibogamine tended be saturable--i.e., elimination would be slow at first and then gain momemtum. Ibogaine may even actually be de-methalated by enzymes within the brain, where nor-ibogaine may behave "as if trapped in the brain" due to the different electrical charge on the ibogamine.
Mark Molliver said glial cell activation in his primates was minor, and the kind of Purkinje cell damage seen in rats so rare that he concluded neurotoxicity is not important in primates. But he saw a syndrome of withdrawal/respiratory slowdown leading to collapse and death--an outcome that could be obviated by massaging the animal to bring it around. And the doses he was using (150 mg./kg. 5 times every 2 1/2 hrs.) caused seizures. Molliver also gave neurotox results in monkeys on 12-hydroxy-ibogamine, which turned out to have "only a fraction" of the toxicity of Ibogaine itself--though in all the same sites, in the Purkinjes of the cerebellar vermis and so-on. It was also strongly hypotonic,* [*ataxic, sleep-inducing] not tremorigenic like Ibogaine. But brain levels reached this extraordinary inverted "V"-shaped peak because nor-ibogaine passed easily into the brain and then couldn't get out, at least not very fast. What this presented was a new, pharmaco-dynamic picture of the "splitting of skull": of the 12-hydroxy-ibogamine punching through--and abruptly reversing--the oscillating Ibogaine effect, and then reaching a sharp peak for a few hours in the brain before falling off in line with the ending of the visions. So a distinct interval of cerebellar reset, if any, might lie in this moment of discontinuity between the effects of drug and metabolite, not the transition from normal wakefulness to drug.
The trend was clear: even though some of the animal toxicities were horrendous, at therapeutic levels Ibogaine is non-neurotoxic in humans, and nor-ibogaine even less so. In animals high doses are toxic--increasingly so as researchers moved from primates to the rat and dog, but only at prolonged exposures, which might be generating distinct toxic metabolites.
The persistence of 12 hydroxy-ibogamine in the brain may also be the key to Ibogaine's "re-set" of endorphin levels from the chronic deficity of heroin addiction. According to finings of Dzoljic, the weak by long-lived nor-ibogaine effect on all three opiate recptors potentiates production of endogenous nor-harman, the neurotransmitter of eidetic memory and dreams-- in effect 'fooling the system' because another of the active metabolite's effects, like nor-harman, is itself to reverse to reverse built-up tolerance, so receptors can tehn signal normal production of endorphins to resume. In fact, Lotsof believes nor-harman is also the body's first line of defense against opiate addiction, but that without help from the metabolite, it is simply overwhelmed by heroin.
On the other hand, these kinds of "mixed," agonist/antagonist effects with Ibogaine (tremorgenic, kappa-ergic, with NMDA binding attnuated by sigma-2 activity) raise the interesting possibility that Ibogaine both potentiates and paritailly antagonized the effects of its active offspring nor-Ibogaine (hypotonic, serotonergic, weakly active at the mu and delta, as well as kappa and NMDA sites--but not at sigma-2). This is because glutamate and glycine are necessary to "unlock" the NMDA receptor. Therefore NMDA activity and any modulatory sigma-2 effect must entrain with Ibogaine's rhythmic (10-times-a-second) glutamate firing, driven by the olivo-cerebellum. And during the peack, visualization phase, Ibogaine tremore is shunted into "flickering" back and forth between Ibogaine and nor-ibogaine modes, which subjects experiences as "two world super-imposition"--as the sigma-2 pulse of the more potent Ibogaine momentarily brings them down from their Iboga/serotonin dream ["I had only to open my eyes and I was back in the room"] attentuating the NMDA channel bloccker effect and letting in a nano-pulse of calcium.
Adam N., recently re-interviewed, provided the add itional insigt that the process of working the aches out of one's body for several days after a treatment may be fairly integral to the successful interruption of opiate dependence. Just as some kind of prolonged up-regulation of nor-harman by lingering iboga metabolite my be necessary for the successful "re-set" of endorphin receptors, this upsurge of endorphins cuased by tremor-induced body aches that settle in at the beginning of of the introspective period--following after peaks of Ibogaine and 12 hydroxy-ibogamine--my put opiate addicts on the pharmaco-kinetic equivalewnt of a glide-path to receptor re-set. Indirect evidence of such an effect is seen in the longer recovery times Lotsof notes that heroin and methadone addicts seem to need after Ibogaine, compared to the relative ease with which cocaine abuser recover.
Stanley Glick, pursuing the antithetical notion that the interrupter effect is independent of tremor, reports that coronaradine and racimic ibogamine (both non-tremorigenic) interrupt morphine self-administration in rats. Mash, likening nor-ibogaine to a long-acting opiate, tole OMNI magazine, "If craving returns to some extent in some people, it may be because Ibogaine's metabolite are washing out over time. Maybe we'll need something after Ibogaine for maintainance."
But if nor-ibogaine and other iboga compounmds are non-competitive NMDA antagonists, like Ibogaine and harmaline, then lthe proper area of inquiry leads into aspects of learing and reorganization of long-term memory that can only be studied in humans. A long-lasting NMDA noncompetitive antagonist metabolite that lingered in the brain might explain the "delayed recall" effect where events from an Ibogaine experience may still snap into focus weeks or even months after a treatment.
Aika hyvältä paketilta vaikutti myös tämä
http://www.drugrehabwiki.com/wiki/Ibogaine
Deborah Mashilla on tosiaan tällänen patentti1 How Ibogaine Got Its Start in the U.S.
2 How Ibogaine Gains Wider Interest from Respected Medical Community
3 Dr. Mash Discovers Noribogaine, an Active Metabolite of Ibogaine
4 Clinical Testing of Noribogaine
5 Dr. Mash Holds Patents for Metabolite - Noribogaine
6 How Noribogaine Works
7 Future of Noribogaine
8 Warning About Underground Clinics for Ibogaine
9 Further Reading
Noribogaine In The Treatment Of Pain And Drug Addiction - Patent 7754710
http://www.docstoc.com/docs/58173016/No ... nt-7754710
Sitten löytyi vielä toistaiseksi melko hiljaiselta vaikuttava ibogaforumi
http://www.ibogafoundation.com/forum/in ... ad04176f05&
