PubMed · 6972605
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J M Gatti. 1981-02-20. [Analgesics].. https://pubmed.ncbi.nlm.nih.gov/6972605/
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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.
The cardiopulmonary effects of romifidine at 80 microg/kg (R80) or 120 pg/kg (R120), and detomidine at 20 pg/kg (D20) when used as premedicants for ketamine/halothane anaesthesia were investigated in six ponies. Using a blinded crossover design, acepromazine (0-04 mg/kg) was administered followed by the alpha-2 agonist. Anaesthesia was induced with ketamine at 2.2 mg/kg and maintained with halothane (expired concentration 1.0 per cent) in oxygen for three hours. During anaesthesia, arterial blood pressure, cardiac index, PaO2 and PmvO2 decreased, and systemic vascular resistance and PaCO2 increased. The cardiac indices for R80, R120 and D20 were, respectively, 39, 39 and 32 ml/kg/minute at 30 minutes and 29, 29 and 26 ml/kg/minute at 180 minutes. The alpha-2 agonists had similar cardiovascular effects, but PaO2 was significantly lower with R120. The quality of anaesthesia was similar in all three groups.