Synthesis and binding affinity of cis-(-)- and cis-(+)-N-ethyleneamino-N-nordeoxymetazocine and cis-(-)-N-normetazocine analogues at sigma1, sigma2 and kappa opioid receptors.
The synthesis of cis-(+)- and cis-(-)-N-ethyleneamino-N-nordeoxymetazocine and cis-(-)-N-normetazocine analogues is described and their affinities to sigma1, sigma2 and kappa opioid receptors are evaluated. The cis-(+)-deoxy compounds displayed high sigma/kappa selectivity with nanomolar K(i) values for sigma1 receptors, whereas in the cis-(-)-N-normetazocine series the compound (-)-7b was found to bind with nanomolar affinity to the kappa opioid receptor (K(i)=21.5 nM). Compound (-)-7b showed good selectivity for the kappa opioid receptor in comparison to the sigma1 and sigma2 sites and to the mu and delta opioid receptors. A correlation of the binding affinities between cis-(-)- and cis-(+)-N-deoxynormetazocine derivatives show that both isomers of the deoxy analogs have similar sigma1 and sigma2 binding profiles as the cis-(+)-N-normetazocine derivatives.
Ronsisvalle
G
G
Department of Pharmaceutical Sciences, University of Catania, Viale A. Doria, 6, 95125, Catania, Italy. ggrmedch@mbox.unict.it
Prezzavento
O
O
Marrazzo
A
A
Vittorio
F
F
Bousquet
E
E
Di Toro
R
R
Spampinato
S
S
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009019:Morphinans / Q000138:chemical synthesis / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017480:Receptors, sigma / Q000187:drug effects*; D013237:Stereoisomerism; D000097605:Sigma-1 Receptor
D007202:Indicators and Reagents; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor