Raphael Mechoulam Interview Part 6


About Raphael Mechoulam

Raphael Mechoulam (Hebrew: רפאל משולם‎) (born 1930) is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of Δ9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.

Transcript: These two receptors that are specific to cannabinoids. But cannabinoids also, some of them bind to other receptors. There is one-called 133 I think, GPR133, there is another one, which is GPR18. I may be mistaken on the numbers, but I think GPR18, GPR133 and so on.

They are not specific for the cannabinoids so there is a lot of discussion between the pharmacologists should we call them cannabinoid receptors. The decision at the moment is lets wait and sees. At the moment we have only two that have been approved as cannabinoid receptors. All the others with a question mark.

Two receptors have evolved for certain specific conditions, feeding for example, appetite, feeding, and things of that sort. But some of the other actions most definitely go through other systems. We do not know enough and where they, a lot of compounds, endogenous compounds, which do a huge number of things. For example tomorrow, I will be talking about a compound which is chemically is very closely related to Anandamide, yet, it does not bind to the receptor, but it has quite a few other effects. Its a vaso-relaxant for example, thats important, because when one gets a head injury, many things happening at the same time. One of them is vaso-constriction, this compound is a vaso-relaxant and is produced by the brain, and chemically its very close to Anandamide but it doesn’t bind to the cannabinoid receptor.

There are other things for example, in the bone we have endogenous compounds like R2AG, which acts and lowers the damage of Osteoporosis. It increases osteoblats, and reduces osteoplasts. (which receptor does this go through?). CB2, well mostly CB2, it acts on CB1 as well, but not directly, indirectly. But we have an additional compound. For example in the bone, we are speaking about bones, there is a compound, Oliel-Seerin which is chemically related to Anandamide but it does not bind to the receptor, and yet it lowers the damage of osteoporosis.

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