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Herkinorin

T

theblueletters

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Jan 11, 2006
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http://en.wikipedia.org/wiki/Herkinorin

Synthesis from Salvia Extracts? Two Steps with relatively decent conversions.

Anyway its Kappa affinity goes down 50 fold and its Mu affinity goes up 25 fold from Salvia. Delta goes way up as well but still in a range that isnt significant when the other numbers are considered.

From Primary Source
benzoate 13 and nicotinate 14 were synthesized.
Introduction of the benzoyl group (13) resulted
in a 47-fold loss of affinity at kappa receptors compared to 1
(Ki ) 90 nM vs Ki ) 1.9 nM). Surprisingly, this
modification resulted in a 25-fold increase in affinity at
Mu receptors compared to 1 (Ki ) 12 nM vs Ki > 1000
nM) and a 5-fold increase in affinity at ä receptors
compared to 1 (Ki ) 1170 nM vs Ki ) 5790 nM).
Click to expand...
 
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I've read that paper and it's definitely interesting. The morphine rule doesn't even seem applicable to herkinorin. The two steps seem relatively easy, but I don't know how useful salvia will be as starting material, especially considering its ever-shrinking legality. I've yet to develop the skills to fully interpret binding affinty data, does anyone know how potent this actually is? 25 fold sounds decent, but does salvinorin A have appreciable mu binding in the first place? If this is indeed viable, I'd be very interested to hear first hand accounts, especially with regards to the development of tolerance.
 
I thought morphine's MOR affinity was ~7.5nM ( i am really unsure of this actually, i need to check)..
 
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Seeing as you can't have a 25 fold increase from zero, I'm left thinking it must have some affinity, as "25-fold increase in affinity at Mu receptors compared to 1 (Ki ) 12 nM vs Ki > 1000 nM)" seems to suggest. Although 12nM from something greater than 1000 nM is a lot more than a 25x increase by my math. Assuming herkinorin is a full mu agonist, as salvinorin a is for kappa, could one then speculate that while salvinorin with a 1.9 nM Ki (for kappa) and full effects seen at around 1mg, that herkinorin may show full effects at around, say 6.3mg, since its Ki for mu is 12 nM? Let my guess, no, you need IC50, bioavailability, and host of other forms of data and its then still worthless speculation without some real bioassays (in the human animal, of course). ;)
 
I think its interesting that tolerance doesn't develop in the same way as it does in other opioids. Wonder if this means less physical withdrawal?
 
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