Acyclic analgesics

In the original paper the proposition was made that the receptor of Fig. 13.4, formulated on the basis of the morphine molecule, was capable of accommodating other structural types of analgesic, and a common mode of drug-receptor interaction for both cyclic and acyclic analgesic molecules was implied. These aspects are now examined in the light of the more extensive evidence and data now available. 

Many conformational options are open to acyclic analgesics like methadone and the thiambutenes, and it is not unlikely that some may have an aromatic and basic group suitably aligned for association at the morphine-... 

The concept of multiple uptake modes of ligand-receptor interaction arose from studies of acyclic analgesics of the basic anilide type 34 and was first clearly delineated by Portoghese.(71) These anilides differ from the general... 

Acyclic analgesics Methadone (9) Levomethadyl acetate Propoxyphene (10) Available as generic Orlaam (Roxane) Darvon-N (napsylate) (EliLilly), available as generic (HCl) i.m., S.C., p.o. with individualized dosing p.o. with individualized dosing p.o. 10 20 130-200 ... 

More radical dissection of the morphine molecule was in progress concurrently with the work above. The chemistry of the series of analgesics that rely on an acyclic skeleton, the compounds related to methadone, is discussed earlier. Suffice it to say that this series of agents, with the possible exception of propoxyphene, seem to share abuse and addiction potential with their polycyclic counterparts. 

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... 

PHENYLPIPERIDINES, PYRROLIDINES AND RELATED COMPOUNDS ACYCLIC AND MISCELLANEOUS CLASSES ANTAGONISTS OF ANALGESICS... 

All compounds that behave as narcotic analgesics characterized by the usual criteria contain a basic nitrogen center that either forms parts of an alicyclic ring system, as in morphine and pethidine, or terminates an acyclic chain, as in methadone, etonitazene, and the enkephalins. Nonbasic compounds of high activity in antinociceptive tests invariably fail to satisfy criteria for narcotic analgesics, such as reversal of effects by naloxone or nalorphine or evidence of binding to opioid receptors recent examples are the barbiturate... 

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