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Eur J Pharmacol. 1994 Mar 3;253(3):R7-8.

Blockade of U50,488H analgesia by antisense oligodeoxynucleotides to a kappa-opioid receptor.

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  • 1Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.


The recently cloned kappa-opioid receptor has binding characteristics consistent with those of a kappa 1-opioid receptor. Repeated intrathecal administration of an antisense oligodeoxynucleotide against the kappa 1-opioid receptor selectively lowers U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetemide) analgesia (P < 0.02) without affecting mu or delta analgesia. A mismatched antisense oligodeoxynucleotide in which 4 bases had been switched is inactive against U50,488H analgesia. These studies confirm at the molecular level traditional pharmacological studies implying a distinct receptor mechanisms for kappa 1 analgesia and demonstrate the utility of antisense approaches in studies of opioid pharmacology.

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