The Neuroscience and Pharmacology Quick Question Thread

[izo]

i though there was a similar thread already, but no. if there are enough question one could make it a sticky thread, could be helpful for some.

 

[izo]

does anybody know where you can compare sequence homology of human receptors? i know there is at least one site, but i forgot. Vector should know.^

 

[sekio]

maybe a tool like BLAST ?

 

[izo]

thanks. next question: when do alkylhalides become toxic due to beiing alkylators? i suppose this is just the case for bromo- and iodoalkanes?

 

[4meSM]

thanks. next question: when do alkylhalides become toxic due to beiing alkylators? i suppose this is just the case for bromo- and iodoalkanes?

When?
I suppose you could say that those alkylating agents become toxic when they're able to get to the nucleus and easily react with one or multiple nucleobases (adenine is usually easier to alkylate) forming DNA adducts that can't be properly repaired by the cell. Or maybe they can be repaired but the process ends up creating more issues down the road (over/underexpression of
enzymes, epigenetic changes, etc...).

Many electrophilic compounds have the potential to alkylate DNA, I would put primary alkyl chlorides among them as well until proven otherwise.
Some electrophilic compounds may not be able to react with DNA, but they will react with multiple proteins... Sometimes the body will able to deal with them (before or after the reaction takes place) and sometimes it won't.
I would personally avoid ingesting any reactive alkyl halide though.

But in both cases the alkylation process takes place via a nucleophilic substitution reaction which can be an SN1 or an SN2. The electrophile will react with a NH2 group from DNA or with cysteine residues (thiol group) from proteins. Other amino acid residues can sometimes be alkylated as well, mainly serine via its hydroxy group, but that's rare AFAIK.

 

[izo]

ah ok, thanks.

i meant when along the line of halogens, so that eg fluoro and chloroalkanes dont work as alkylating agents when ingested due to their higher electronegativity and that this only becomes a problem with bromo and iodoalkanes.

 

[Skorpio]

ah ok, thanks.

i meant when along the line of halogens, so that eg fluoro and chloroalkanes dont work as alkylating agents when ingested due to their higher electronegativity and that this only becomes a problem with bromo and iodoalkanes.

I definately would view a chloroalkane with suspicion of being an alkylator.

Fluoroalkanes should be fine.

 

[izo]

i just asked myself if the head twitch response of mice is just to serotonergic psychedelics or does this also happens when mice get dissociatives?

 

[izo]

another quick question: ive heard that cocaines cardiotoxicity stems from one of the two ester groups but i forgot which one it was. my bet would be on the benzoyl ester but im not sure.

 

[plumbus-nine]

i just asked myself if the head twitch response of mice is just to serotonergic psychedelics or does this also happens when mice get dissociatives?

Interesting question, I'd say no but not too sure. They're still using dissociatives (PCP) as an animal model for schizophrenia even when I so far only found people telling that dissos are not schizo-mimetic, also it's kind of accepted now that chronic, not just acute NMDAr blockade is required for schizo-like symptoms to set in, which I'd agree to. I got some positive symptoms (auditory hallucinations) from prolonged disso abuse, but also got seriously intoxicated from bad batches' impurities more than once and I could easily imagine these god-knows-what toxic substances being at least partially responsible for, as things recovered even with me continuing using dissociatives - required abstinence though for to really heal. Still, they were using amphetamine as a schizo model before, and stimulants didn't trigger anything in me, while DXM - the only reliable trigger - does. DCK not, memantine (high dose) slightly but not reliably so. Maybe the brains of humans and mice are too different from each other to reliably extrapolate anything psychedelis-related. Animals don't self-administer psychedelics, for example, even when they don't have our prejudices or care about illegality of substances, so they should have less risk of catching a bad trip - then again, the set these rats are kept in is anything else than ideal for a trip, so maybe they really just don't self-administer out of bad trips. Imagine being a lab rat which suddenly realizes he's a lab rat, whoa dude. There's this nice theory about DMT having been a relevant factor in the development of consciousness.

 

[izo]

i have a new question: on the german wikipedia page for the Horner-Wadsworth-Emmons-Reaction it is stated that the phosphonate stabilized carbanion is a stronger nucleophile but a weaker base relative to the ylid in the wittig reaction. how can that be? i thought that stronger nucleophile automatically means also a stronger base...

 

[sekio]

i thought that stronger nucleophile automatically means also a stronger base...

the two are related but do not correlate 1:1 always

 

[izo]

Is there a Sequence homology between the sigma, nmda and kappa receptor? Thanks.

 

[Skorpio]

I would think very little.

Kappa opioid receptors are pretty classical GPCRs and have 7 trans membrane helices that share a lot of homology with the other opioid receptors (and less but still quite a bit of homology with other gpcrs), the sigma receptors are super weird (two transmembrane helices and a single extracellular loop), NMDA receptors have four subunits forming a heterotetrameric channel with a lot of the receptor's bulk situated extracellularly.

Here are papers discussing the crystal structures of the proteins.

NMDA structures - https://sci-hubtw.hkvisa.net/10.1038/nature13548

Sigma receptor structure - https://sci-hubtw.hkvisa.net/10.1038/nature17391

Kappa opioid receptor - https://sci-hubtw.hkvisa.net/10.1038/nature10939

 

[izo]

ive got a phenomenon with 3-mec that i never had with any other drug: i take it orally or rectally and need 50-70mg max, its mediocre. i take it nasally and its fully active at 15-20mg, feels like methylone and i have a great time. what this? my wonder noose?

 

[izo]

why not try doc lowdose for dementia and stop this piracetam bullshit?

 

[izo]

Is there any way you can oxidize the cyclohexene ring of tetrazepam to plain phenyl by any viable means?

 

[izo]

Ok another question: does anybody know why psylocin (4ho-dmt) goes so much Better through the blood-brain barrier than bufotenine (5ho-dmt). I suppose it’s the permeability of said barrier that makes for the difference in duration and dose needed.

 

[Fertile]

Hydrogen-bonding between the 4-OH and the -NH2.

 

[izo]

Thanks.