x1

10mg Parnate (4 days before) + ~1mg Abilify (from weeks before) + 5-10mg Memantine + Zolpidem PRN, + Dextroamphetamine 7.5mg 2-3x + Diphenhydramine 20mg + Carbamazepine (from weeks before) .25 of pill

Peroxynitrite and Amphetamine / Meth Neurotoxicity

Ann N Y Acad Sci. 2001 Jun;939:366-80.
Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts.
Imam SZ, el-Yazal J, Newport GD, Itzhak Y, Cadet JL, Slikker W Jr, Ali SF.

Neurochemistry Laboratory Division of Neurotoxicology, HFT-132, National Center for Toxicological Research/FDA, 3900 NCTR Rd., Jefferson, AR 72079, USA.
Abstract
Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5, 10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-sulfonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions.

PMID: 11462792 [PubMed - indexed for MEDLINE]

Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.
Imam SZ, Islam F, Itzhak Y, Slikker W Jr, Ali SF.

Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Abstract
Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

Brain Res. 1999 Aug 7;837(1-2):15-21.
Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst.
Imam SZ, Crow JP, Newport GD, Islam F, Slikker W Jr, Ali SF.

Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Rd., Jefferson, AR 72079, USA.
Abstract
Methamphetamine (METH)-induced dopaminergic neurotoxicity is believed to be produced by oxidative stress and free radical generation. The present study was undertaken to investigate if METH generates peroxynitrite and produces dopaminergic neurotoxicity. We also investigated if this generation of peroxynitrite can be blocked by a selective peroxynitrite decomposition catalyst, 5, 10,15, 20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and protect against METH-induced dopaminergic neurotoxicity. Administration of METH resulted in the significant formation of 3-nitrotyrosine (3-NT), an in vivo marker of peroxynitrite generation, in the striatum and also caused a significant increase in the body temperature. METH injection also caused a significant decrease in the concentration of dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) by 76%, 53% and 40%, respectively, in the striatum compared with the control group. Treatment with FeTMPyP blocked the formation of 3-NT by 66% when compared with the METH group. FeTMPyP treatment also provided significant protection against the METH-induced hyperthermia and depletion of DA, DOPAC and HVA. Administration of FeTMPyP alone neither resulted in 3-NT formation nor had any significant effect on DA or its metabolite concentrations. These findings indicate that peroxynitrite plays a role in METH-induced dopaminergic neurotoxicity and also suggests that peroxynitrite decomposition catalysts may be beneficial for the management of psychostimulant abuse. Copyright 1999 Published by Elsevier Science B.V.

PMID: 10433983 [PubMed - indexed for MEDLINE]
Selenium, an antioxidant, attenuates methamphetamine-induced dopaminergic toxicity and peroxynitrite generation.
Imam SZ, Ali SF.

Neurochemistry Laboratory, Division of Neurotoxicology, HFT-132, National Center for Toxicological Research/USFDA, 3900 NCTR Road, Jefferson, AR 72079, USA.
Abstract
Methamphetamine (METH) has been known to produce neurotoxicity via generation of reactive oxygen and nitrogen species. Selenium, an antioxidant, was reported to protect against METH-induced dopaminergic neurotoxicity in mouse caudate nucleus. In the present study, the in vitro and in vivo efficacy of the supplementation of selenium was studied in METH-induced generation of peroxynitrite. PC12 cell cultures were exposed to 200 microM METH either with or without 10 microM and 20 microM selenium (30 min prior to METH exposure). After 24 h, METH exposure resulted in the significant depletion of dopamine, and its metabolites DOPAC and HVA, as well as the significant formation of 3-nitrotyrosine (3-NT), a marker of peroxynitrite generation, in PC12 cell cultures. Selenium supplementation attenuated the depletion of dopamine and its metabolites, DOPAC and HVA and the formation of 3-NT in PC12 cells. For in vivo studies, adult male mice were supplemented with selenium in drinking water, 1 week before and 1 week after the multiple injections of METH (4x10 mg/kg, i.p. at 2-h interval) or an equivalent volume of saline. The supplementation of Se attenuated the formation of 3-NT in the striatum resulting from METH treatment. These data suggest that METH-induced neurotoxicity is mediated by the production of peroxynitrite, and selenium plays a protective role in METH-induced neurotoxicity.

http://www.ncbi.nlm.nih.gov/pubmed/11085318

Memantine and Amphetamine / Methamphetamine Neurotoxicity / Tolerance

J Pharmacol Exp Ther. 2005 Nov;315(2):658-67. Epub 2005 Aug 2.
Methyllycaconitine prevents methamphetamine-induced effects in mouse striatum: involvement of alpha7 nicotinic receptors.
Escubedo E, Chipana C, Pérez-Sánchez M, Camarasa J, Pubill D.

Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Nucli Universitari de Pedralbes, Universitat de Barcelona, Spain.
Abstract
In a previous study, we demonstrated that in rat striatal synaptosomes, methamphetamine (METH)-induced reactive oxygen species (ROS) production was prevented by methyllycaconitine (MLA), a specific antagonist of alpha7 neuronal nicotinic acetylcholine receptors (alpha7 nAChR). The aim of this study was to test the influence of MLA on acute METH effects and neurotoxicity in mice, using both in vivo and in vitro models. MLA inhibited METH-induced climbing behavior by 50%. Acute effects after 30-min preincubation with 1 microM METH also included a decrease in striatal synaptosome dopamine (DA) uptake, which was prevented by MLA. METH-induced neurotoxicity was assessed in vivo in terms of loss of striatal dopaminergic terminals (73%) and of tyrosine hydroxylase levels (by 90%) at 72 h post-treatment, which was significantly attenuated by MLA. Microglial activation [measured as 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide binding] was also present at 24 h post-treatment and was fully prevented by MLA, tending to confirm its neuroprotective activity. MLA had no effect on METH-induced hyperthermia. Additionally, flow cytometry assays showed that METH-induced ROS generation occurs inside synaptosomes from mouse striatum. This effect implied release of vesicular DA and was calcium-, neuronal nitric-oxide synthase-, and protein kinase C-dependent. MLA and alpha-bungarotoxin, but not dihydro-beta-erythroidine (an antagonist that blocks nAChR-containing beta2 subunits), fully prevented METH-induced ROS production without affecting vesicular DA uptake. The importance of this study lies not only in the neuroprotective effect elicited by the blockade of the alpha7 nicotinic receptors by MLA but also in that it proposes a new mechanism with which to study METH-induced acute and long-term effects.

PMID: 16076935 [PubMed - indexed for MEDLINE]Free Article

more rapping stuff

Tranylcypromine
Its not quite what it seems
But what I really thought it means
The name is powerful, it seems
When I was in my teens
On me people leaned
I hoped that, Tranylcypromine
Would make me clean
But nevertheless
What i take, doesn’t work
Thus Im permanently banned
To forums where I lurk
I see facebook pictures
Of girls I like
Sometimes, sometimes
My hope is in sight
But the light, the end of the tunnel
I can see it, sometimes it gets really bright
But I cant take it lightly, or ill let it out of my sight
Cuz I don’t got might but I do got fight
At least a little bit, I know ill still slip
the lord seems to help if I go under and flip
So I don’t have to sit, I don’t have to quit
Ill just keep trying, cuz im not a piece of shit
Or should I think I am, because if so, then
I wouldn’t ever get stuck up, but then my pen
It likes to rhyme, it doesn’t like to push away
The truth flows outta me when I pray, or I say
So help me lord, I know you hear my prayer,
I know you see me hiding in my makeshift lair
I know its not fair, but I’m tired of my cares
Just take my shares, just help me up the stairs
You know I cant do this, by myself ill miss it,
I ve got no power, I always fail so I diss this
Im an empty, open book, ready too get took
Just open your arms wide, and take a big look
I really do need you , even if I forget
I don’t wanna get punished, but I know ive got debt
Just please let, fill me and make me set
Make me wanna do your work, make me fly like a jet
You know your cool, you know im a fool,
You know when im in pain, I will fall down and drool
You know Im a dual personalitied fellow
With a conscience and heart, as bendable as jello
You got this lord, help me trust that you will do so
Let my hope and my joy, outta my actions let it flow
make my eyes glow, my personality show
Your love and power, let them see it, and know.

Im a sickly, frail dude.
I got hope, and i try to keep trying
. ..hoping that someday, everything,
will be, MORE than just ok.
Im tired of lying, all this fake rhyming.
pretending it has a point......but,.
who cares? haha........everybody cares
they all wanna help me, they put in the effort
and they never gonna shelf me....i got
unlimited support, and quite a few resor---
--sez, its a shame , that theres no, one to blame
but myself, for my situtations stagnant air,
but you say, you always ask, why I sit right there
every day, every way, it dont matter what you say i always-
-stay, in my shell, but...you see, I DO care--- theres a
rift, inbetween, reality-assuming
when you make, a mistake, its cuz you were presuming-----

what you see, sometimes don't, correlate too well
to the truth of what that is, whats inside, that shell
what you see, is the opposite of what , im implying
whats white, is really black, whats true...I am denying.

Theres various ways, that we use today
To solve our problems , this is what I say
With insight, and, an algorithimic way
Right now im gonna tell u what I learned today
An algorithim is a very logical rule
Guarantees, a solution , even if u a fool
But insight, its different, it’s the inverse rule
Its illogical, its abstract , a lot more cool

Heuristic describes a thinking strategy
It helps u make judgments more efficiently
U can solve a problem, without much as much effort
but its more error prone, but faster in court

than the algorithmic way, I learned today
Confirmation bias is a kinda lame way
that we----confirm our perceptions, and our preconceptions
to support our false claims , it’s a dangerous way

justification, your own obliteration,
that’s the kinda stuff that gets to destroy nations
but it can be fixed, if your willing to change
the way you think, ….but u wont, that’s why its really kinda strange

fixations inability to look at a problem
from a another perspective , its keeps u from solve them
be u stubborn, its just the human way
u stick to your mindset, u think its ok

mental set, a way to do a problem
the same old way, every single time u solve them
its developed by your past ones, turning out successful
cuz u wouldn’t do a thing, that could might be distressful

functional fixedness, is a concrete way
the tendency to think things ina concrete way
screwdrivers cant ever do nothing else
never can they be a way to do something else

it just gets so old, every day im being told----------------that i
cant do a thing cuz it aint fit the mold-------of my
teaching, bleaching my fake affiliation of my
nations’ belief that we all be creations



but….I know that you see, that there is more to me
a lot more to me, than simply just what you see
the reason I asks cuz im not quite free ,
I assure you when I am, youll see the real me
Ive always been messed up ever since I can remember cuz i
Member in december I was 5 …………..cant find no rhymes no more.
I was good be 4, but I always want more
It don’t matter what its for, its always seem like it’s a chore ……….i always
Wait till the last chance the very point at which I cant
Become what I want to be, shun, that which isn’t me
Trust in him who comforts me, and choose the choice that makes me free I
Hate that which I have become, I hate this never having fun
Complicated such it is, I don’t know why I cannot say, why
I, am a helpless dude. I function like a selfish prude
I Think im always right (of course)
Help me Lord? Can you afford it?
If you can afford me, it'd be nice if you'd restore me..

I just had to act, in front of quite a few people….but it
Wasn’t very hard..I acted crazy,
i dont know quite why, i still get nervous, cuz
my whole life, Ive ALWAYS been crazy

well the real thing is, i dont really know
i didnt read the papers, my knowledge is quite low
im taking xanax for anxiety, my thinking is slow
so im just spitting out words as randomly as a crow

michael jackson died, its quite a sad thing
i thought he would be happy, with his car and his bling
but maybe he got tired of the duty to sing
he realized fame, its not really that great of a thing

it can wear you down, it can crush your spirit
if you screw up your rep, its impossible to clear it
so why dont you just chill, go to the couch and sit
and let me make my rhymes right and let me make them rip

cuz im so tired of 2009, its always the same, everything outta line
theres never enough time, never enough rhymes, never enough
energy to make the big climb,
outta the economic depression, in which we now reside
we spent too much money, we let our credit scores slide
way down to the bottom, our fleeting joy we ride
until we get bankrupt, then not evenour friends on our side

you see we all are like sheep, we follow each other
then when we get a little mad, we murder our brothers
we take everything for granted, we dont listen to our mothers
then we wonder why life sucks, why we feel so smothered

were a decrepit society, its common knowledge all right
the light at the end of the tunnel, is not quite in sight
but if we really do try, with all our feeble might
maybe we can fix the blight, get us outta the night

cuz were the USA, united states of america
supposedly the strongest nation in the world
but unless we change, the way we do what we do
our realities gonna end up swirled you see

we need a god to fix us, to give us a lift
we need more people to care, like the people on night shift
working hard for their families, about to fall from the cliff
we need to turn to the lord jesus, and eat a spoonful of Jif*

*Jif peanut butter on graham crakers is really good

what i do in psychology class

This is another rap, that im writing in class
I cant pay attention, my cognition wont last
Too many obstructing factors, distractions , of such mass
I cant concentrate on stuff, I cannot think too fast
Stanford-Binet is a type of test
To measure intelligence, so we could figure out, lest
The original test, which was made by Binet
Was revised by Terman (Stanford University) next.
Eugenics is what, were gonna talk about next
It’s a 19th century, phenonmenon, yes
They wanna gather good genes, and waste all the bad
Genetics sometimes results in survival of the best….i guess?
They inhibited people, from reproducing,
Constituting, suppression of ability of choosing
If you wanna make babies, its up 2 your own musing
But the battle 4 freedom, looks like, you are, losing
This is the only thing I do, I cant quite push through
I hafta write this rap, its kinda crip-crew ish
My legs just keep twitching, my OCD snitching
Conformations impossible, plausible, for you……
My mind just wont stop, but my grades, they still flop
Im always tyrna my best to produce, a good crop
Back to the classroom, what sometimes seems like…doom,
But I like it much more, than solitude, in my room
Ok , now more notes, on psycho logy istic ness, yes
Intelligence quotients, aren’t used no more today, yes
Apparently they failed, aint describe the sole truth
Its like saying junk food, aint described by Babe Ruth
That’s the candy bar….im referring to, the one covered in chocolate
Intelligence described, the ability to learn
From experience , to adapt, to learn from the past
To apply information, to novel situations
Make connections inbetween, knowledge and stipulations
Its really hard to measure right, my concern of such, is light
I must admit, I don’t care, much, bout which person is right
Especially if its bout a meaningless fact, or tidbit
Of information, ….. im done, with enunciation

http://tips-for-new-bloggers.blogspot.com/2007/02/add-music-to-blogspot-blog.html

Wiki Rap, props to Kobie

This is a rap about a dude name kobie

Who started out editing wiki quite slowly

He made numerous articles, about lotsa drugs (meds)

But drugs don’t mean he was wunna the thugs (heads)

So he wikied all night and he wikied all day

he made so many edits , I don’t know what to say

on the internets, while other dudes got laid

but his work it aint been recognized till today

So I say, if I may, that theres no other way

That id still be alive, and legit, to this day

If it werent 4 that wiki site, itd be more than just gay

Your like “whys he talking bout this,? Just listen, ok……

We got 15 grand, 15 grand,

We got no other dude, who in such high demand

He went to Bluelight, that sites tight, but then he got panned

Cuz Hammilton popped, (he thought he owned that phat land)

But that don’t matter if we focus on the latter

After all, aren’t we all a bunch of lifeless matter?

Why does it matter, If that dude is fatter ---cuz we

Crippin people act like we mad as a hatter

Editing articles left and right, he gettin

PubMed citations, this stuff aint light, see

This expertise, sometimes its kinda nice

Learning psychopharma via decapitated mice

No, that don’t entice, but at least were being nice

Don’t you realize, everythings comes at a price?

But we tryna be ethical, we got synaptic vesicles

These mice be getting bupe, b4 they go 2 the vice

There last minutes gotta be, the best of their lives

400X dopamine has gotta be nice

They haterz say we tripping, but we, we just be sippin

On the purple drank straw, cuz the Law aint our Life

You gotta understand, sometimes, that life demands

Deviation, if u ever wanna live, somewhere close to elation

It’ll always be more than just the right combination,

It don’t matter how many corrupt drug corporations

If you got no hope, you better raise yo expecations…

Cuz its ghetto, right here in the

psychopharmaceutical nation