TY - JOUR
T1 - Sigma receptors mediate the psychotomimetic effects of N-allylnormetazocine (SKF-10,047), but not its opioid agonistic-antagonistic properties
AU - Khazan, N.
AU - Young, G. A.
AU - El-Fakany, E. E.
AU - Hong, O.
AU - Calligaro, D.
N1 - Funding Information:
Supported by NIDA Grant DA-01050. Thanks are plying us with the isomers of SICK-10,047.
PY - 1984/8
Y1 - 1984/8
N2 - Our present findings suggest that SKF-10,047, the prototype sigma agonist, has its opioid entity residing with its (-) isomer, while both Its (+) and (-) isomers possess psychotogenic properties similar to those produced by PCP. We found that (-)-SKF-10,047 blocks EEG and behavioral effects of morphine in the naive rat, precipitates withdrawal in morphine-dependent rats, produces physical dependence as evidenced by naloxone-induced withdrawal, and displaces [3H]dihydromorphine from brain homogenates. (+)-SKP-10,047 did not produce dependence upon chronic treatment, and it did not displace [3H]dihydromorphine from brain homogenates. Such pharmacodynamic dissociation with SKF-10,047 suggests an association of sigma receptors with psychogenic, but not opioid effects. The latter are most likely mediated by mu or kappa receptors.
AB - Our present findings suggest that SKF-10,047, the prototype sigma agonist, has its opioid entity residing with its (-) isomer, while both Its (+) and (-) isomers possess psychotogenic properties similar to those produced by PCP. We found that (-)-SKF-10,047 blocks EEG and behavioral effects of morphine in the naive rat, precipitates withdrawal in morphine-dependent rats, produces physical dependence as evidenced by naloxone-induced withdrawal, and displaces [3H]dihydromorphine from brain homogenates. (+)-SKP-10,047 did not produce dependence upon chronic treatment, and it did not displace [3H]dihydromorphine from brain homogenates. Such pharmacodynamic dissociation with SKF-10,047 suggests an association of sigma receptors with psychogenic, but not opioid effects. The latter are most likely mediated by mu or kappa receptors.
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U2 - 10.1016/0028-3908(84)90015-7
DO - 10.1016/0028-3908(84)90015-7
M3 - Article
C2 - 6090969
AN - SCOPUS:0021284195
SN - 0028-3908
VL - 23
SP - 983
EP - 987
JO - Neuropharmacology
JF - Neuropharmacology
IS - 8
ER -