Beckett-Casy

Extensive molecular dissection of the morphine molecule over the past several decades led to a host of molecules which showed narcotic analgesic activity even though they possessed but faint suggestion of the structural features present in morphine itself. Thus, both cyclic molecules such as meperidine (70) and alphaprodine (71), and acyclic Compounds such as methadone (72) were found to be effective analgesics. Common features of these compounds were formalized by the Beckett-Casy rule, which states as minimal required structural features (a) an aromatic ring attached to... 

In the above section, we described the C16-N17 bond cleavage reaction of naltrexone derivative 35 that gave oxazolidinone derivative 36 without a D-ring (Scheme 15). This cleavage reaction prompted us to reinvestigate the Beckett-Casy... 

The present knowledge on the subject is that there are at least four different receptors with which morphine can interact, three of which are analgesic receptors. The initial theory on receptor binding assumed a single receptor site, but this does not invalidate many of the proposals which were made. Therefore, it is informative to look at the first theory—the Beckett-Casy hypothesis. 

The previous theory tried to explain analgesic results based on a single analgesic receptor. It is now known that there are several different analgesic receptors which are associated with different types of side-effects. It is also known that several analgesics show preference for some of these receptors over others. This helps to explain the anomalies resulting from the previous Beckett-Casy hypothesis. 

Figure 5-14. Relationship of morphine to Beckett-Casy receptor.

Beckett, A.H. and Casy, A.F. Synthetic analgesics Stereochemical considerations, J. Pharm. Pharmacol. 1954, 6, 986-1000. 

AH Beckett, A F Casy, and N J Harper, J Pharm Pharmacol 8, 874 (1956), and refs there cited... 

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