Dialkylaminoalkylnaphthalenes as novel opioid-like analgesics.
The study of dialkylaminoalkylnaphthalenes as novel opioid-like analgesics is reported. In particular, the synthesis of (1R,2R/1S,2S)-1-ethyl-1-[2-(6-hydroxynaphthyl)]-1-hydrox-2-m ethyl-2-dimethylaminoethane and its structural analogue (1R,2R/1S,2S)-1-ethyl-1-[2-(6-fluoronaphthyl)]-1-hydroxy-2-methyl- 2-dimethylaminoethane and the configurational analysis by X-ray and 1H NMR spectroscopy are described. Pharmacological profiles are discussed on the basis of the experimental results of analgesia tests (hot plate and writhing test) and rota-rod test, which was performed to distinguish analgesia from drug-induced motor changes. The compounds showed dose-dependent antinociception, with less potency than morphine. Motor coordination appeared to be less involved.
Collina
S
S
Dipartimeto di Chimica Farmaceutica, Università di Pavia, Italy. collina@chifar.unipv.it
Azzolina
O
O
Vercesi
D
D
Benevelli
F
F
Callegari
A
A
Tadini
C
C
Lanza
E
E
Barbieri
A
A
Ghislandi
V
V
D000701:Analgesics, Opioid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism; D013055:Spectrophotometry, Infrared
D000701:Analgesics, Opioid; D009281:Naphthalenes; D011957:Receptors, Opioid