PubMed · 10483316
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A Kopf. 1999. [Formulary].. https://doi.org/10.1024/0040-5930.56.8.465
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The present experiment was designed to investigate the dose-effect and time-effect functions of the kappa-opioid receptor agonist [5alpha,7alpha, 8beta)-(-)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4, 5)dec-8-yl]benzeneacetamide] (U69,593) in intact and gonadectomized male and female rats as a function of hotplate temperature (45 degrees C or 51 degrees C). At 45 degrees C baseline lick latencies were longer in female rats than in male rats. Lick latencies increased dose-dependently in all subjects except intact female rats. U69,593 increased lick latencies as a function of time since its administration in all subjects. At 51 degrees C baseline lick latencies did not differ between groups and they increased dose-dependently in all subjects. The effectiveness of U69,593 decreased as a function of time since its administration, but not in castrated male rats. These observations suggest that gonadal hormones could play a role in modulating the behavioral effects of U69,593 when subjects are tested at different hotplate temperatures.
The position of the indole in the indolomorphinans, which includes the delta opioid antagonist naltrindole, is considered to be responsible for the delta opioid selectivity for this class of ligands. Herein is described the N-cyclohexylethyl substituted N-nor-derivative, which is shown to be mu preferring. Thus, the nature of the N-substituent is equally important to the receptor selectivity for this class of ligands.
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