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      Comparison of the Duration of Action of Nalmefene and Naloxone on the Hypothalamic-Pituitary Axis of the Rhesus Monkey

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          Abstract

          The duration of action of nalmefene, a relatively new opiate antagonist, on the hypothalamic-pituitary axis of the rhesus monkey was compared to that exhibited by naloxone. Ovariectomized monkeys (n = 5) were pretreated with 10 mg nalmefene, 10 mg naloxone or an equivalent volume of saline 12, 24, or 48 h prior to the administration of 10 mg morphine. Blood samples were collected by venipuncture 0, 1,2,3 and 4 h after injection of morphine and were assayed for luteinizing hormone (LH) and prolactin (PRL). Duration of action of these two opiate antagonists was estimated from their ability to block morphine inhibition and stimulation of LH and PRL release respectively. Morphine reduced serum LH concentration by 60% and increased PRL levels approximately 4-fold in saline-pretreated animals. Administration of nalmefene either 12 or 24 h, but not 48 h prior to morphine, significantly antagonized the effects of this opiate on LH and PRL release. In contrast, naloxone at all pretreatment intervals failed to block morphine’s effect. We conclude that a single 10 mg bolus injection of nalmefene exerts significant activity at the opiate receptors that mediate the effects of morphine on LH and PRL release for at least 24 h after administration, whereas the same dose of naloxone has a duration of action less than 12 h. Based on this finding it is likely that the effects of endogenous opioid peptides in the rhesus monkey can be chronically antagonized by the daily administration of nalmefene.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1989
          1989
          02 April 2008
          : 49
          : 3
          : 275-280
          Affiliations
          aDivision of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, and bDepartment of Physiology, Queen’s University, Kingston, Canada
          Article
          125128 Neuroendocrinology 1989;49:275–280
          10.1159/000125128
          2716954
          © 1989 S. Karger AG, Basel

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          Page count
          Pages: 6
          Categories
          Original Paper

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