Synthesis and pharmacologic properties of 6-succinylcodeine.
In our search for a ligand to be used for affinity chromatography in the separation of putative, codeine-specific receptors, we have synthesized a pharmacologically active codeine derivative, 6-succinylcodeine (Ib). The structure of the compound has been confirmed. It is markedly less toxic than the parent compound, codeine (Ia), and has significantly weaker antitussive properties in the cat. On the other hand, its antinociceptive properties in the mouse and effects on guinea pig ileum are comparable to those of codeine. An interesting pharmacological property of Ib is its hypotensive effect in both cats and rhesus monkeys. The compound has been successfully coupled to an aminoalkyl agarose matrix. When coupled to the matrix, the drug loses its capacity to cause contraction of the guinea pig ileum but this property is restored upon alkaline hydrolysis of the coupled beads. Whether the diminished antitussive properties, as compared to the parent compound, or the loss of capacity to inhibit guinea pig ileum contractility when coupled to agarose would limit its usefulness for affinity chromatography of codeine-specific receptors is being investigated.
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
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E
Toro-Goyco
P C
PC
Zenk
U
U
Estrada
J F
JF
Kachur
L S
LS
Harris
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000996:Antitussive Agents / Q000138:chemical synthesis*; D002415:Cats; D002855:Chromatography, Thin Layer; D003061:Codeine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D000996:Antitussive Agents; C054877:6-succinylcodeine; D003061:Codeine