Friday seminar; Dr Prisinzano on Salvia Divinorum

I attended the seminar this Friday where Dr. Prisinzano from the University of Kansas gave a presentation on his research with the plant Salvia Divinorum.  The plant is known for its hallucinogenic properties when smoked and Dr. Prisinzano's work with the isolated psychoactive compounds has shown a lot of promise for medicinal uses.  He gave quite a few details on how the compounds can be manipulated through organic reactions and how the smallest changes can make a large difference in how effective it was.  In one instance he showed how the receptors for this compound preferred a certain stereochemistry at one of the asymmetric centers, and changing that made it much less effective.  He discussed how the compound was insoluble in water which is a problem that must be overcome for medicinal use.  
Of the many reactions he went over in manipulating the compound only a few were familiar to me with what we have covered so far in studying organic chemistry.  In one case a Diels-Alder reaction was used to add a ring to the compound.  A lot of what we learned this week with the Palladium catalyst Pd(PPh3)4 and Suzuki reactions were used in the synthesis reactions he went over.  
One of the biggest differences between this compound and opiates or other alkaloids was that it does not contain a basic Nitrogen in the compound; which was thought to be necessary to interact with opioid receptors.  This makes the compounds derived from the plant Salvia Divinorum unique and opens up a lot of new possibilities.  Dr. Prisinzano went into a lot of detail on research done with one derivative called Herkinorin which was experimented with on rats.  Herkinorin acts as an analgesic and the study showed that it does not have the same problems that other opiates have with tolerance.  The rats grew an extreme tolerance to morphine and was not effective unless the dose was increased.  The problem Dr. Prisinzano outlined is that you can only do this so much until it kills you, so there is a "ceiling" with the dosing.  Herkinorin did not seem to have the problems of tolerance that morphine had in the rats and implicates huge benefits in medicine.  This was one of the aspects Dr. Prisinzano focused on the most but it seems that research done on other derivatives could open up a lot more possibilities.  He also showed how over 60% of drugs since the early 1980's were derived from natural origins.  
This was the first seminar I have attended and I found it very interesting and plan on going to more this semester.  I would encourage anyone in our class to attend one of these if the topic interests you.