An animal model of schizophrenia based on chronic LSD administration: old idea, new results.
Marona-Lewicka D, Nichols CD, Nichols DE.
Neuropharmacology. 2011 Sep;61(3):503-12. Epub 2011 Feb 23.
http://dx.doi.org/10.1016/j.neuropharm.2011.02.006
This is not really earthshattering research or anything, but it is interesting to see that administration of LSD to young rats over extended periods of time induces prolonged psychosis. This provides some support of the permanent effect of psychedelic drugs as HPPD.
I am on the beg for (I hope) the last time. Some years ago I found a paper which discussed the QSAR of a series of novel kappa agonists. Well, as you may know, the difference between mu & kappa ligands is that the latter has an extra methylene spacer. Someone put the kappa patent on Scribd, but since I wasn't totally up on kappa ligands, I wasn't SURE I could modify to make a mu ligand.
Well, the team behind the kappa ligands have released a paper on the mu ligands of the same class.
Design, synthesis and biological evaluation of 3-amino-3-phenylpropionamide derivatives as novel μ opioid receptor ligands
The lead compound is thus:
Image propanamide hosted in ImgBB
ibb.co
Now, it only has 4 of the 5 key moieties and it's only 14 methylenes in length. Now, the opbious solution would be to lengthen the 1-phenylethyl moiety to a 1-phenylpropyl BUT that introduces and extra rotatable carbon bond and I assume that this LOWERS potency. From notes, a 3-cinnamyl chain the middle carbon-bind is olefinic i.e. -CH=CH- but this then placed the beta benzene ring in the wrong position.
As it is, the compound cotains 4 of the 5 key moieties and I am willing to bet that borrowing a trick from BDPC, a p-Br is added to the alpha benzene thus:
Image propanamide hosted in ImgBB
ibb.co
There examples with a m-OH (phenol) on the alpha benzene ring but these a mixed agonist/antagonists but since this compound closely overlays BDPC, ad p-Br seems likely. It was Lednicer who identified the optimum biosteric minumum for mu agonists - 15.
There are related compounds like ciramadol but the m-OH yields mixed agonist/antagonist activity. I could never find the paper but their is a ciiramadol homologue which replaces mixed activity with pure mu agonist. In that case, replacing the m-OH with a p-Cl has been made and tested and is a stimulating opioids. I dare say that the 3,4-dichlori derivative will be even more potent.
There are still more opioids that have been lost to the depths of time I intend to visit the Bodlian with a massive number of references to hunt down.
While I have said all of this, I also deeply interested in GMO. GMO opium poppies, GMO cannabis (lots of HC but none for the stuff that causes severe side-effects.
My last aim is to provide VERY safe opioids and to write a book on the subject. Pyrazolam was chosen because it can be made in 3 steps.... and the immediate precursors is available. OK I will also seek to improve on pyeyzolam (by adding a second benzo thar produced effects almost indistinguishable from ethano....
But their is always room for research.
Oh, and look out for etofixine or more likely an etofixine derivative - while not EXACTLY like alcohol, it's really nice, really safe and water soluble so it can be put into drinks (and I do not mean spiking.
I could go on and and on but I see people are bored.
But I am always keen for people to ask questions not found in an educational system.
The payoff> I know a few people whose mental health has been destroyed with LSD and I feel that we should do more to help.