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Ketamine salts solubility

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Okay. Let's give this a whirl:

Endogenous Positive Allosteric Modulation of GABAA Receptors by Diazepam binding inhibitor
Catherine A. Christian1, Anne G. Herbert1, Rebecca L. Holt1, Kathy Peng1, Kyla D. Sherwood1, Susanne Pangratz-Fuehrer1, Uwe Rudolph2, John R. Huguenard1:

Abstract:
Benzodiazepines (BZs) allosterically modulate γ-aminobutyric acid type-A receptors (GABAARs) to increase inhibitory synaptic strength. Diazepam binding inhibitor (DBI) protein is a BZ site ligand expressed endogenously in the brain, but functional evidence for BZ-mimicking positive modulatory actions has been elusive. We demonstrate an endogenous potentiation of GABAergic synaptic transmission and responses to GABA uncaging in the thalamic reticular nucleus (nRT) that is absent in both nm1054 mice, in which the Dbi gene is deleted, and mice in which BZ binding to α3 subunit-containing GABAARs is disrupted. Viral transduction of DBI into nRT is sufficient to rescue the endogenous potentiation of GABAergic transmission in nm1054 mice. Both mutations enhance thalamocortical spike-and-wave discharges characteristic of absence epilepsy. Together, these results indicate that DBI mediates endogenous nucleus-specific BZ-mimicking (“endozepine”) roles to modulate nRT function and suppress thalamocortical oscillations. Enhanced DBI signaling might serve as a therapy for epilepsy and other neurological disorders.

at ScienceDirect: http://www.sciencedirect.com/science/article/pii/S0896627313003577
doi: http://dx.doi.org/10.1016/j.neuron.2013.04.026
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ebola
 
My last SO was a blue lighter....wasnt too interested in the add side of things though...
 
The HIV antiretroviral drug efavirenz has LSD-like properties.

Abstract:
Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz depress open field activity in a novel environment. In rats trained to discriminate LSD from saline, efavirenz substitutes for LSD, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild type, but not 5-HT2A-knockout mice. Despite having GABAA potentiating effects, like benzodiazepines and barbiturates, and interactions with DAT, SERT and VMAT2, like cocaine and methamphetamine, efavirenz fails to maintain self-administration responding in rats that maintain cocaine self-administration responding, and it fails to produce a conditioned place preference. Though its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates in part with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.Neuropsychopharmacology accepted article preview online, 24 May 2013; doi:10.1038/npp.2013.135.
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This one really surprised me, and can't be that common. How much spare efavirenz can there be for people to "crush the pills and smoke the powder for its psychoactive effects"?
 
there have been reports of people abusing HIV meds for hallucinogenic properties, primarily in africa, since the mid-2000s. i dont think its a new thing.

in africa where the prevalence of hiv is probably high, it would be easy to get some antivirals...
 
sekio said:
there have been reports of people abusing HIV meds for hallucinogenic properties, primarily in africa, since the mid-2000s. i dont think its a new thing.

in africa where the prevalence of hiv is probably high, it would be easy to get some antivirals...
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Yea I think you're right. There's a bunch of press reports of people being robbed of their meds after leaving HIV clinics in africa. You'd think anyone prescribed an antiretroviral would rather take it for its intended purpose than to trip out for a while.

The new finding here is that efavirenz subjective effects are LSD-like and not anything-else-like.
 
Oh, and I got the article (thanks!), and please feel free to PM me if you want a copy.

ebola
 
central nervous system;cocaine- and amphetamine-regulated transcript;receptors;signalling pathway
Summary
1. Cocaine- and amphetamine-regulated transcript (CART), first isolated from the ovine hypothalamus, is a potential neurotransmitter widely distributed throughout the central and peripheral nervous systems, as well as in endocrine cells in the pituitary and adrenal glands, pancreatic islets and stomach.

2. Numerous studies have established the role of CART in food intake, maintenance of bodyweight, stress control, reward and pain transmission. Recently, it was demonstrated that CART, as a neurotrophic peptide, had a cerebroprotective against focal ischaemic stroke and inhibited the neurotoxicity of β-amyloid protein, which focused attention on the role of CART in the central nervous system (CNS) and neurological diseases.

3. In fact, little is known about the way in which CART peptide interacts with its receptors, initiates downstream cascades and finally exerts its neuroprotective effect under normal or pathological conditions. The literature indicates that there are many factors, such as regulation of the immunological system and protection against energy failure, that may be involved in the cerebroprotection afforded by CART.

4. The present review provides a brief summary of the current literature on CART synthesis and active fragments, its distribution in the CNS and, in particular, the role of CART peptide (and its receptors and signalling) in neurological diseases.



http://onlinelibrary.wiley.com/doi/...sCustomisedMessage=&userIsAuthenticated=false
 
All of their experimental ligands seem to be unknown "in the wild". However, I'm not sure whether the studies detailing the activities of mono-fluoro-amphetamines have screened for activity as direct agonists.

ebola
 
sekio said:
Not a journal article but interesting anyway

Derek Lowe - Chemical probes vs drugs

-snip-

Makes me think about, say, the NBOMes versus LSD.
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I'd like to think that more selective drug-like compounds would ultimately and necessarily mean better drugs. If any non-selective drug is effective due to interacting with multiple targets, then would those effects not be achievable with a cocktail of individual ligands?
 
Yes, but then instead of one ADME problem, you have n ADME problems that all depend on each other... unless those agents are perfectly selective and don't touch each others metabolism, you're probably better off with a monotherapy.
 
Cognitive Neuroscience

Hi ADD,

Was unsure where to post this, but I felt this would be the most appropriate place to ask - you intelligent bunch! I'm a postgraduate sports & exercise scientist who has decided to pursue a master's in Cognitive Neuroscience. I want to purchase some books to help form the foundational knowledge necessary for Cognitive Neuroscience. My questions are A) What are the best books to purchase? B) Where is the cheapest place to buy them? Keeping in mind that I am from the UK.

If there is a forum better suited then feel free to move, but I thought you guys would have the best knowledge for this question.

Many thanks,

JW.
 
Well it all depends on what your current knowledge is. Do you know any cell biology, brain physiology, or pharmacology? Not trying to be redundant I swear!
 
Epsilon Alpha said:
Well it all depends on what your current knowledge is. Do you know any cell biology, brain physiology, or pharmacology? Not trying to be redundant I swear!
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My knowledge is ok, but I really need to go back to the basics and learn things indepth for a thorough core understanding. I have some understanding about the serotonergic system, central executive functions (I conducted a dissertation on this - exercise & cognition) & the neurobiology of addiction as this area intrigues myself. In areas, my knowledge is advanced and in others its non existent. I just want a solid book which provides the foundational knowledge.

Thanks for your help.
 
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