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Erowid/BlueLight Neuropharmacology Text

endotropic said:
Hmm strange, I'll make sure sekio knows the imageshack link isn't working. In the meantime you can access the text by clicking through the links in the original post on this thread.
Click to expand...

Why didn't I try that? I must have been really tired...
Thanks!
 
Cognocyclopedia

So I have a MS in neuropsychopharm and do neuro research as a career. I'm an expert in cell signaling, molecular bio, addiction, drugs (of many types), pharmacology, proteomics (protein interactions), structural and organic chemistry, etc.

I'd love to help contribute to this 'organic' reference mine of real knowledge from people who don't prescribe or advertise molecules, but actually have experience with them. I've always believed patients know more about their conditions, their drug, and their Brody than the doctor does, and especially the govt.

There are corrections in some of the postings, though, I'd like to make. The definition of a protein is incorrect and more akin to an enzyme. A protein is one of ~22 amino acids that contain a NH2 amine end and a COOH carboxylic end. Tyrosine, phenethylamine, tryptophan, histidine, serine, asparagine...those are small molecule proteins. They can bind together at the N terminal of one and the C terminal of another to form a peptide bond. The order in which they are assembled is encoded in our DNA and so, too, our mRNA. When created, methionine is always the first to be made, and there can be hundreds-thousands of polypeptide bonds. The structures form grooves, helices, and sheets. They always have an active site now that they are enzymes. All enzymes are proteins, but not the other way around. Enzymes serve a catalytic purpose in all cellular functions. The majority add phosphate groups to molecules and other enzymes or macroproteins. A simple protein, however, is generally no more than 8 carbons and 1 nitrogen with some hydrogens and occasionally 1-2 oxygens or 1 sulfur.

Proteins are building blocks for either enzymes, vitamins, or neurotransmitters. Drugs, too, are made from proteins or based on their structure. For example, amphetamine is an acronym. aLPHA-mETHYL-phENetHTYL amine.
Look at amphetamine and phenethylamine and you'll understand why adderall affects the dopaminergic pathway how it does.

It's important to know the epinephrine and adrenaline are the same molecule, but have different names depending on how our body uses them. Adrenaline is a hormone whereas epinephrine is a neurotransmitter.

I'd love to have s chapter in misnomers and misunderstandings--i.e. Oxy is NOT synthetic heroin. Firstly...they are two different molecules made from different molecules. Secondly, 'synthetic' in this sense does not apply to chemistry. If THC was made in a lab or grown on the plant, it is still THC. 'Synthetic' can only be used in terms of how a molecule is made rather than its resemblance to another drugs effect (sorry, but peeve of mine).

Other examples would be separating adderall from meth stigma. I think it's important to talk about race if mixtures as well. A lot of people think that Dexedrine is significantly stronger than adderall. But adderall is actually 75% d-amphetamine...not 50% like some people think. Ritalin is also more similar to cocaine than adderall regarding its mechanism of action. Heroin is not bad (or any worse than any other potent opioid). It's street heroin that's dangerous and our laws that make H 'bad.' When norco or Percocet say 10/325...that means 10mg of drug, 325 Tylenol. So many people tell me they have the '500mg kind of vicodin.' Also...opiates are only the naturally occurring compounds like morphine, thebaine, and codeine. Opioids are any drug that binds to the delta/kappa/mu-opioid receptors. Mm benzodiazepines are f'ing dangerous. Don't take them unless you need to. Do not get dependent (it would be cool to define addiction, tolerance and dependence from a cellular modification perspective). BZD withdrawal is unbearable. GABA (along with glycine) is our only inhibitory compensatory mechanism in our brain. Don't mess with it or your brain will be repleted with excitotoxic NMDA-mediated glutamatergic transmission which will lead to apoptosis/cell death. Alcohol too. Finally for now, be your own advocate. Doctors truly are poorly educated on pain mgmt or psych disorders. Research your meds, if you want to change them, find an intelligent way of communicating why. For example, despite it being a recognized beneficial practice, docs don't do it because they don't like change and because the dea might think something is wrong--if you are on a long term treatment (i.e. Narcs or BZDs), you can mitigate tolerance and delay/avoid severe dependence if you frequently alternate your med with one similar to it. Switch from klonopin to Ativan to Valium or Xanax and back to klonopin. Each of these drugs binds to a different GABAa subtype, so you will never down-regulate one receptor through over stimulation for more than a month before switching. The same goes for roxi/perc, zohydro, dilaudid, morphine (oral BA sucks), or Opana. Stay away from bup or methadone unless it's for maintenance/detox. Talk with your doc. Save your receptors!

Uh so yeah. Hit me up or reply. Let me know if I can help craft this thing ;) Salúd, friends
 
Ps-the advice i offer was only for educational and harm reduction purposes. I do not encourage the misuse or specific use of any substance in particular.
 
The link don't work for me.
Just links to imageshack - no book.

Anyone have an updated link?
 
BilZ0r said:
I contacted erowid recently, with the proposal to write a text that would hopefully bring the laymen up to a reasonable standard, as far as neuropharmacology/neurophysiology goes, in regards to psychoactive drugs.

The erowid team replied, saying that they would love it.

What I'm now proposing to you guys, is that we write it. I suggest that a single person is asked to write a section/chaper (hopefully one you're familiar with). Erowid suggested using a Wiki, and I think that after we've written it up in posts in here, we can port it over to one, and link it all up.

The chapter layout I proposed to erowid basically looked like this

-What is a cell (BilZ0r)
---What is a Neuron? (ksi and BilZ0r)
-What is a Protein?
---How proteins are produced (crOOk and BilZ0r)
-----What is a receptor? (BilZ0r)
-----What is an Enzyme? BilZ0r)
-Electrical properties of the Neuron (BilZ0r)
---Ion Channels
-----Voltage Gated Ion channels (BilZ0r)
-----Ligand Gated Ion channels (BilZ0r)
-Chemical properties of the Neuron
---The synapse (BilZ0r)
---G-Protein Coupled Receptors, and signalling cascades (BilZ0r)
---Homeostasis in Neuronal Signalling (BilZ0r)

Special Topics
-Pharmacokinetics (BilZ0r)
-Learning, memory and addiction on a cellular level (BilZ0r)
-Monoamine transporters and the amphetamines (BilZ0r)
-GPCRs under the microscope (mitogen)

Drug Glossary

And then maybe some special topics, like neurotoxicity, or anything a particular contributor has a zest for (so long as its appropriate).

Right, so do I have any volunteers? Any suggestion on changing the chapter structure

Printable PDF available here
http://img208.imageshack.us/img208/489/bluelightneuropharmacolmk2.pdf
Click to expand...


I'm doing my dissertation for my Masters in Neuro-Psychopharmacology this year. I have to hand it in in November. When I do I will also forward it through to you or reply to you via private message or the likes.

It will be worth your perusal.
 
Severe depression was I born that way?

BilZ0r said:
Ligand gated ion channels

Ligand gated ion channels are, as their name suggests, channels in a cells membrane that are gated by ligands, i.e. drugs/chemicals. The physiological role of nearly all ligand gated ion channels is to receive chemical signals in the way of neurotransmitters (discussed further in the synapse), and to transduce them to electrical signals. In order for these ion channels to be gated by a neurotransmitter, they have a receptor for the specific neurotransmitter as part of the proteins that make up the receptors. Therefore the ion channel complex is often refereed to by the name of the neurotransmitter/chemical/drug which is has a receptor for, and for the rest of this chapter we will largely use this style.

The two most common types ligand gated ion channels (also called ionotropic receptors) are the ion channels that are opened by the neurotransmitters glutamate and GABA, or ionotropic glutamate and GABA receptors. The ionotropic glutamate receptors may be further divided up into AMPA, kainic acid and NMDA receptors (named after drugs that specifically activate these types). While it is possible to further subdivide these receptors based on the individual proteins that make them up, it is outside the scope of this text. AMPA and kainic acid receptors are generally similar; both are opened by glutamate and both are largely selective for the flow of Na+ ions, which in all physiological situations is into the neuron. This flow of Na+ depolarizes the cell, making it more positive and bringing it closer to the threshold for firing an action potential. Because of this, it can be said that AMPA and kainic acid receptors are “excitatory”. The NMDA receptor is an anomaly amongst ligand gated ion channels, in that it is also partially voltage gated. The channel of the NMDA receptor has a site in which Mg2+ ions can sit. This Mg2+ is much larger than the normal ions that flow through the NMDA receptor (Na+ and Ca2+) and hence blocks it. When the cell partially depolarized, positive Mg2+ ions begin to be pushed out of the NMDA receptor channel (presumably because of the positive charge inside the neuron repelling it). Also, because the NMDA receptor is very permeable to Ca2+ channels, not only does it depolarize (excite) the cell, it also can cause many of the chemical changes within the cell caused by Ca2+ (see G-Protein Coupled Receptors, and signalling cascades). Largely, it is the release of glutamate, and its action of ionotropic glutamate receptors that allow one cell to excite another cell into firing (although usually it requires 100s of cells to release glutamate onto a cell to cause this).

The most famous drugs which directly effect ionotropic glutamate receptors are the so called “anaesthetic dissociates”, e.g. ketamine, PCP and DXM. These drugs all block the NMDA receptors ion channel, i.e. they are NMDA channel antagonists. Alcohol's actions is thought to be at least in part due to its ability to block NMDA receptor channels (Woodward, 2000).

The ligand gated ion channel that is gated by GABA is called the GABA-A receptor (to distinguish it from the non-ion channel GABA-B receptor). This channel is largely selective for the transit of Cl- ions. As stated before, Cl- ions have a reversal potential of around -60mV, so if a cell has a resting membrane potential of around –60mV GABA-A receptors do not cause much of an effect on membrane potential i.e. they neither hyperpolarise nor depolarise the cell. But if the cell is being depolarised by the action of ionotropic glutamate receptors, then GABA-A receptors strongly oppose this, and hence its action is often referred to as inhibitory).

A wealth of drugs directly effect GABA-A receptors, specifically benzodiazepines and barbiturates which bind to sites apart from the GABA binding site or the channel, to increase channel opening only when GABA normally opens the receptor. This is an example of allosteric modulation, and is a common feature of ligand gated ionc channels. Muscimol is a direct agonist, acting like GABA. Alcohol is also though to stimulate GABA-A receptors, though whether this is a direct action is still debated (Aguaya et al., 2002)

There are other kinds of ligand gated ion channels, though the only ones which have much relevance to recreational drugs are the ionotropic acetylcholine and serotonin receptors, also called the nicotinic and 5-HT3 receptors. Both of these receptors are ligand gated sodium channels. Nicotine activates the nicotinic receptor, and serotonin, which could be released by the action of MDMA, can activate 5-HT3 receptors (which may cause MDMA-induced vomiting). There are also the glycine, P2X and VR1 ligand gated ion channels expressed in the central nervous system.

As you can see, ligand gated ion channels are an important (probably the most important) mechanism of neuron-to-neuron communication, and drugs acting on this form of chemical to electrical transmission have a powerful way to alter neuronal activity (discussed more in Signalling properties of neurons).

References
Woodward JJ. Ethanol and NMDA receptor signaling. Crit Rev Neurobiol. 2000;14(1):69-89.


Aguayo LG, Peoples RW, Yeh HH, Yevenes GE. GABA(A) receptors as molecular sites of ethanol action. Direct or indirect actions? Curr Top Med Chem. 2002; 2(8):869-85.
Click to expand...
great stuff I have severe depression and do remember being a tad depressed as a child before use question is did my drug use make it worse and how without a substance can I make my electricical grid fire and just be able to get out of my own way of thinking. I am scared I have destroyed my neroulogical circuit what natural none mind altering route to the happy life do I have?
 
It's sort of crazy, a few years ago I was reading this thread, trying to better understand the processes that take place in the brain that give rise to the vast psychoactive and psychological states that we experience. I was lost in a sea of unfamiliar words and novel concepts.
This week I will be attending my graduation from uni in neuroscience, and I know a lot of the topics like the back of my hand.
Amazing how life comes full circle. :)
 
BilZ0r said:
I contacted erowid recently, with the proposal to write a text that would hopefully bring the laymen up to a reasonable standard, as far as neuropharmacology/neurophysiology goes, in regards to psychoactive drugs.

The erowid team replied, saying that they would love it.

What I'm now proposing to you guys, is that we write it. I suggest that a single person is asked to write a section/chaper (hopefully one you're familiar with). Erowid suggested using a Wiki, and I think that after we've written it up in posts in here, we can port it over to one, and link it all up.

The chapter layout I proposed to erowid basically looked like this

-What is a cell (BilZ0r)
---What is a Neuron? (ksi and BilZ0r)
-What is a Protein?
---How proteins are produced (crOOk and BilZ0r)
-----What is a receptor? (BilZ0r)
-----What is an Enzyme? BilZ0r)
-Electrical properties of the Neuron (BilZ0r)
---Ion Channels
-----Voltage Gated Ion channels (BilZ0r)
-----Ligand Gated Ion channels (BilZ0r)
-Chemical properties of the Neuron
---The synapse (BilZ0r)
---G-Protein Coupled Receptors, and signalling cascades (BilZ0r)
---Homeostasis in Neuronal Signalling (BilZ0r)

Special Topics
-Pharmacokinetics (BilZ0r)
-Learning, memory and addiction on a cellular level (BilZ0r)
-Monoamine transporters and the amphetamines (BilZ0r)
-GPCRs under the microscope (mitogen)

Drug Glossary

And then maybe some special topics, like neurotoxicity, or anything a particular contributor has a zest for (so long as its appropriate).

Right, so do I have any volunteers? Any suggestion on changing the chapter structure

Printable PDF available here
http://img208.imageshack.us/img208/489/bluelightneuropharmacolmk2.pdf
Click to expand...
Please add "Psychopharmacology ".
 
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