Talk:Dizocilpine
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Olney's lesions?
[edit]The article sats this: "MK-801 had a promising future as a neuroprotective agent until neurotoxic-like effects were seen in certain brain regions." Does this have to do with Olney's lesions or something else? If so, I can cite this, but otherwise, we need a citation for this. Jolb 21:34, 7 January 2007 (UTC)
- The harm I know of that MK801 causes is neurovacuolization. And there could be other studies that found toxicity. I know MK801 didn't do too hot in clinical trials because it has poor tolerability, e.g. causing intense, unpleasant aural hallucinations. Here's the ref I've found for the vacuolization thing, I'll go ahead and add it in:
- Olney J, Labruyerre J and Price MT. 1989. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Sciencel, Volume 244, Issue 4910, Pages 1360-1362. Accessed January 7, 2007.
- delldot | talk
- Here's another ref: Ellison G. 1995. The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Research. Brain Research Reviews. Volume 20, Issue 2, Pages 250-267. Accessed January 7, 2007.
- delldot | talk
- And another:
- Hargreaves RJ, Hill RG, Iversen LL. 1994. NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology. Acta Neurochir Suppl (Wien). 1994;60:15-9. Accessed January 7, 2007.
- I dunno, should I add this one in too, or would that be overkill? delldot | talk 23:49, 7 January 2007 (UTC)
- Only the link in your second post works for me. The other two link to a search page. Anyway it does seem that these are what I thought, Olney's Lesions. I'm no expert, so you take a look and see if you agree that these are the same... Jolb 02:04, 9 January 2007 (UTC)
- Huh, weird. I can't get the links to work. I don't know what's going on. Have you heard of that happening before, linking to a pubmed source and it not being there? delldot | talk 07:52, 9 January 2007 (UTC)
- Ah HAH! try this for Hargreaves and this for Olney. If that doesn't work, I give up. I'm changing the links in the article. delldot | talk 18:34, 9 January 2007 (UTC)
- If you hear Olney's lesions being touted around at DXM, you'll know that it was cased by injection of MK-801 into rats, and as a NMDA antagonist, it was assumed the all of the antagonists could cause lesions. --68.45.219.63 (talk) 19:03, 6 March 2008 (UTC)
Residual deficits in thinking
[edit]This statement is unsourced. What does it really mean? Permanent? Miserlou (talk) 21:48, 27 November 2007 (UTC)
Lever pressing studies are fundamentally flawed..
[edit]A drug is truly addictive when it interferes with a persons life. For the purposes of a rats, addictive behavior has been noted in the subculture of drug abuse; perhaps this is urban legend, but perhaps "bag rats" - rats will actually risk detection in order to grab mostly empty bags that once held methamphetamine in order to stick their heads in and lick the bags, that live amongst the filth associated with long-term abusers in run down neighborhoods.
That is a sharp contrast from lever pressing behavior; to understand this, one must merely contemplate that the rat in a cage generally has nothing else very exciting to do but press the lever in the first place, and all the challenges of its life, such as obtaining food, safety, and shelter, have already been pre-eliminated by the lab conditions.
The end result is that the lever pressing studies tend to show addictive potential in every instance that a drug is not perceived by the organism to be actually unpleasant. It is entirely possible to construct a lever pressing study that will show that injections of sucrose solution are quite addictive - all you need are bored rats that don't much care for the taste of their otherwise nutritious chow, and therefore slightly undereat it, and will experience a mild "boost" from the sugar injection's raising of blood sugar level... and if you actually let them eat and swallow it, it becomes even more "addictive" ...
Show me rats that will press a lever that causes a mild electric shock half the time, and the other half of the time administers a drug pellet, in an otherwise interesting environment filled with stuff to play with and challenges with rewards (tastier food snacks that require work to obtain, for example), and THEN a drug can be said to be truly addictive to the rat! In the meantime, this article seems to indicate that several human studies or anecdotes suggest strongly that human addicts apparently reject this material as a substance of abuse, which means it is probably not truly an addiction risk. Zaphraud (talk) 19:43, 23 April 2009 (UTC)
re "human experience"
[edit]I have deleted this section. The dosage mentioned was 5mg/kg in humans. This is correctly cited from the given ref. The reason for deleting is: 0.05mg/kg have been described for their behavioral toxicity effects in rats. 10mg/kg has been described as a lethal dosis in rats in the data sheet of the substance. 0.03mg/kg have been described as TDLo in rats. A human fatality has been described in a mixed intoxication with 25mg, but 5mg/kg would be 350mg in a 70kg human! I believe 5mg/kg is a transcription error in the ref and orders of magnitudes off. The same ref descibes dizocilpine as much more potent than PCP, which supports that this could be a transcription error. I do not want some unlucky Wiki reader trying to replicate this "human experience" in himself with a dose that is close to LD100(!) in rats. Humans are usually much more sensitive than rats, who are genetically optimized by nature to eat all kind of stuff like rotten meat and being much more tough little darlings than humans are. I have contacted the author of the ref and asked him to take a look. Please keep it like that until there is better evidence. I believe Wiki policy is against inclusion of dosage in chemical and pharmaceutical articles, in particular in articles and substances like this. 70.137.156.196 (talk) 05:04, 24 July 2011 (UTC)