The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform
Bernard Belleau - One of the best experts on this subject based on the ideXlab platform.
-
Agonist and antagonist opioid activity of axial and equatorial conformations of S-methyl- and S-allyl-Morphinans.
European journal of pharmacology, 1994Co-Authors: Simon Lemaire, Bernard Belleau, François B. JolicoeurAbstract:Abstract Resolved axial (β) and equatorial (α) forms of S -methyl (β-sulforphanol, α-sulforphanol) and S -allyl (β-sulfallorphan, α-sulfallorphan) Morphinans were tested for their ability to depress the electrically evoked contractions of the guinea pig ileum and of the mouse vas deferens, to compete with the binding of prototype ligands selective for μ-, δ-, and κ-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum and to produce analgesia in a rat thermal pain assay. β-Sulforphanol was more potent than α-sulforphanol in the guinea pig ileum (relative potencies of 93% and 29% respectively, as compared with levorphanol). β-Sulfallorphan were both inactive in the guinea pig ileum assay. In the mouse vas deferens preparation, β-sulforphanol and α-sulforphanol had relative potencies of 2.1% and 1.2% as compared with levorphanol, respectively, while the S -allyl Derivatives were inactive. All Morphinan Derivatives displayed marked binding selectivity for μ-opioid receptors but α-sulfallorphan also showed significant binding potency on δ-opioid receptors (12% as compared to levorphanol). The compounds were also tested for their ability to antagonize the biological activity of morphine. In the guinea pig ileum, α-sulfallorphan potently inhibited morphine with a K e value of 41.7 nM. α-Sulforphanol also antagonized morphine but with a smaller potency ( K e = 350 nM). In the mouse vas deferens, no antagonist activity against morphine was observed with any Morphinan Derivative tested at 1 μM. In the rat thermal pain assay, β-sulforphanol (intracisternally, i.c.) was more potent than α-sulforphanol in producing analgesia while the other Morphinan Derivatives were inactive. In addition, α-sulfallorphan displayed potent antagonist activity against the antinoceceptive effect of levorphanol and in this respect it was at least 10 times as potent as β-sulfallorphan. These data indicate that the equatorial conformation of the allyl group in Morphinan Derivatives confers an antagonist property to the molecule while the agonist activity of sulforphanol greatly depends upon the axial orientation of the methyl group.
-
Neurobehavioral evidence for kappa agonist activity of the Morphinan Derivative 14-β-methyl 8-oxacyclorphan [BC (3016)]
Pharmacology biochemistry and behavior, 1991Co-Authors: François B. Jolicoeur, Simon Lemaire, Daniel Ménard, Robert Rivest, Bernard BelleauAbstract:Abstract The purpose of the present study was to determine if the in vivo neurobehavioral effects of the Morphinan 14-β-methyl 8-oxacyclorphan, [BC (3016)], would reflect the kappa agonist activity found in our previous in vitro studies. The effects of intracisternal administration of various doses (10–80 μg) of BC (3016) on body temperature, muscle rigidity, nociception of thermal, chemical and mechanical stimuli as well as its ability to induce catelepsy were examined. The effects of intrathecal administration of the same doses of the compound on reactivity of animals to a thermal stimulus were also assessed. Finally, the ability of BC (3016) to antagonize well known neurobehavioral effects of morphine was investigated. Results indicate that the analgesic properties of BC (3016) resemble those of typical kappa agonists: Intracisternal administration of the drug failed to affect nociception to an aversive thermal stimulus but markedly reduced the reactivity of animals subjected to noxious chemical or mechanical stimuli. On the other hand, intrathecal administration of BC (3016) significantly attenuated nociception of animals to a thermal stimulus. The in vivo neurobehavioral effects of BC (3016) appear to be kappa selective since the drug did not decrease body temperature, increase muscular tone or induce catalepsy, three effects generally attributed to μ agonists. Furthermore, BC (3016) antagonized the immobility, trunk rigidity, catalepsy and analgesia induced by morphine. In summary, the present results reveal that BC (3016) displays a profile of neurobehavioral effects similar to that of well known kappa agonists.
François B. Jolicoeur - One of the best experts on this subject based on the ideXlab platform.
-
Agonist and antagonist opioid activity of axial and equatorial conformations of S-methyl- and S-allyl-Morphinans.
European journal of pharmacology, 1994Co-Authors: Simon Lemaire, Bernard Belleau, François B. JolicoeurAbstract:Abstract Resolved axial (β) and equatorial (α) forms of S -methyl (β-sulforphanol, α-sulforphanol) and S -allyl (β-sulfallorphan, α-sulfallorphan) Morphinans were tested for their ability to depress the electrically evoked contractions of the guinea pig ileum and of the mouse vas deferens, to compete with the binding of prototype ligands selective for μ-, δ-, and κ-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum and to produce analgesia in a rat thermal pain assay. β-Sulforphanol was more potent than α-sulforphanol in the guinea pig ileum (relative potencies of 93% and 29% respectively, as compared with levorphanol). β-Sulfallorphan were both inactive in the guinea pig ileum assay. In the mouse vas deferens preparation, β-sulforphanol and α-sulforphanol had relative potencies of 2.1% and 1.2% as compared with levorphanol, respectively, while the S -allyl Derivatives were inactive. All Morphinan Derivatives displayed marked binding selectivity for μ-opioid receptors but α-sulfallorphan also showed significant binding potency on δ-opioid receptors (12% as compared to levorphanol). The compounds were also tested for their ability to antagonize the biological activity of morphine. In the guinea pig ileum, α-sulfallorphan potently inhibited morphine with a K e value of 41.7 nM. α-Sulforphanol also antagonized morphine but with a smaller potency ( K e = 350 nM). In the mouse vas deferens, no antagonist activity against morphine was observed with any Morphinan Derivative tested at 1 μM. In the rat thermal pain assay, β-sulforphanol (intracisternally, i.c.) was more potent than α-sulforphanol in producing analgesia while the other Morphinan Derivatives were inactive. In addition, α-sulfallorphan displayed potent antagonist activity against the antinoceceptive effect of levorphanol and in this respect it was at least 10 times as potent as β-sulfallorphan. These data indicate that the equatorial conformation of the allyl group in Morphinan Derivatives confers an antagonist property to the molecule while the agonist activity of sulforphanol greatly depends upon the axial orientation of the methyl group.
-
Neurobehavioral evidence for kappa agonist activity of the Morphinan Derivative 14-β-methyl 8-oxacyclorphan [BC (3016)]
Pharmacology biochemistry and behavior, 1991Co-Authors: François B. Jolicoeur, Simon Lemaire, Daniel Ménard, Robert Rivest, Bernard BelleauAbstract:Abstract The purpose of the present study was to determine if the in vivo neurobehavioral effects of the Morphinan 14-β-methyl 8-oxacyclorphan, [BC (3016)], would reflect the kappa agonist activity found in our previous in vitro studies. The effects of intracisternal administration of various doses (10–80 μg) of BC (3016) on body temperature, muscle rigidity, nociception of thermal, chemical and mechanical stimuli as well as its ability to induce catelepsy were examined. The effects of intrathecal administration of the same doses of the compound on reactivity of animals to a thermal stimulus were also assessed. Finally, the ability of BC (3016) to antagonize well known neurobehavioral effects of morphine was investigated. Results indicate that the analgesic properties of BC (3016) resemble those of typical kappa agonists: Intracisternal administration of the drug failed to affect nociception to an aversive thermal stimulus but markedly reduced the reactivity of animals subjected to noxious chemical or mechanical stimuli. On the other hand, intrathecal administration of BC (3016) significantly attenuated nociception of animals to a thermal stimulus. The in vivo neurobehavioral effects of BC (3016) appear to be kappa selective since the drug did not decrease body temperature, increase muscular tone or induce catalepsy, three effects generally attributed to μ agonists. Furthermore, BC (3016) antagonized the immobility, trunk rigidity, catalepsy and analgesia induced by morphine. In summary, the present results reveal that BC (3016) displays a profile of neurobehavioral effects similar to that of well known kappa agonists.
Simon Lemaire - One of the best experts on this subject based on the ideXlab platform.
-
Agonist and antagonist opioid activity of axial and equatorial conformations of S-methyl- and S-allyl-Morphinans.
European journal of pharmacology, 1994Co-Authors: Simon Lemaire, Bernard Belleau, François B. JolicoeurAbstract:Abstract Resolved axial (β) and equatorial (α) forms of S -methyl (β-sulforphanol, α-sulforphanol) and S -allyl (β-sulfallorphan, α-sulfallorphan) Morphinans were tested for their ability to depress the electrically evoked contractions of the guinea pig ileum and of the mouse vas deferens, to compete with the binding of prototype ligands selective for μ-, δ-, and κ-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum and to produce analgesia in a rat thermal pain assay. β-Sulforphanol was more potent than α-sulforphanol in the guinea pig ileum (relative potencies of 93% and 29% respectively, as compared with levorphanol). β-Sulfallorphan were both inactive in the guinea pig ileum assay. In the mouse vas deferens preparation, β-sulforphanol and α-sulforphanol had relative potencies of 2.1% and 1.2% as compared with levorphanol, respectively, while the S -allyl Derivatives were inactive. All Morphinan Derivatives displayed marked binding selectivity for μ-opioid receptors but α-sulfallorphan also showed significant binding potency on δ-opioid receptors (12% as compared to levorphanol). The compounds were also tested for their ability to antagonize the biological activity of morphine. In the guinea pig ileum, α-sulfallorphan potently inhibited morphine with a K e value of 41.7 nM. α-Sulforphanol also antagonized morphine but with a smaller potency ( K e = 350 nM). In the mouse vas deferens, no antagonist activity against morphine was observed with any Morphinan Derivative tested at 1 μM. In the rat thermal pain assay, β-sulforphanol (intracisternally, i.c.) was more potent than α-sulforphanol in producing analgesia while the other Morphinan Derivatives were inactive. In addition, α-sulfallorphan displayed potent antagonist activity against the antinoceceptive effect of levorphanol and in this respect it was at least 10 times as potent as β-sulfallorphan. These data indicate that the equatorial conformation of the allyl group in Morphinan Derivatives confers an antagonist property to the molecule while the agonist activity of sulforphanol greatly depends upon the axial orientation of the methyl group.
-
Neurobehavioral evidence for kappa agonist activity of the Morphinan Derivative 14-β-methyl 8-oxacyclorphan [BC (3016)]
Pharmacology biochemistry and behavior, 1991Co-Authors: François B. Jolicoeur, Simon Lemaire, Daniel Ménard, Robert Rivest, Bernard BelleauAbstract:Abstract The purpose of the present study was to determine if the in vivo neurobehavioral effects of the Morphinan 14-β-methyl 8-oxacyclorphan, [BC (3016)], would reflect the kappa agonist activity found in our previous in vitro studies. The effects of intracisternal administration of various doses (10–80 μg) of BC (3016) on body temperature, muscle rigidity, nociception of thermal, chemical and mechanical stimuli as well as its ability to induce catelepsy were examined. The effects of intrathecal administration of the same doses of the compound on reactivity of animals to a thermal stimulus were also assessed. Finally, the ability of BC (3016) to antagonize well known neurobehavioral effects of morphine was investigated. Results indicate that the analgesic properties of BC (3016) resemble those of typical kappa agonists: Intracisternal administration of the drug failed to affect nociception to an aversive thermal stimulus but markedly reduced the reactivity of animals subjected to noxious chemical or mechanical stimuli. On the other hand, intrathecal administration of BC (3016) significantly attenuated nociception of animals to a thermal stimulus. The in vivo neurobehavioral effects of BC (3016) appear to be kappa selective since the drug did not decrease body temperature, increase muscular tone or induce catalepsy, three effects generally attributed to μ agonists. Furthermore, BC (3016) antagonized the immobility, trunk rigidity, catalepsy and analgesia induced by morphine. In summary, the present results reveal that BC (3016) displays a profile of neurobehavioral effects similar to that of well known kappa agonists.
Daniel Ménard - One of the best experts on this subject based on the ideXlab platform.
-
Neurobehavioral evidence for kappa agonist activity of the Morphinan Derivative 14-β-methyl 8-oxacyclorphan [BC (3016)]
Pharmacology biochemistry and behavior, 1991Co-Authors: François B. Jolicoeur, Simon Lemaire, Daniel Ménard, Robert Rivest, Bernard BelleauAbstract:Abstract The purpose of the present study was to determine if the in vivo neurobehavioral effects of the Morphinan 14-β-methyl 8-oxacyclorphan, [BC (3016)], would reflect the kappa agonist activity found in our previous in vitro studies. The effects of intracisternal administration of various doses (10–80 μg) of BC (3016) on body temperature, muscle rigidity, nociception of thermal, chemical and mechanical stimuli as well as its ability to induce catelepsy were examined. The effects of intrathecal administration of the same doses of the compound on reactivity of animals to a thermal stimulus were also assessed. Finally, the ability of BC (3016) to antagonize well known neurobehavioral effects of morphine was investigated. Results indicate that the analgesic properties of BC (3016) resemble those of typical kappa agonists: Intracisternal administration of the drug failed to affect nociception to an aversive thermal stimulus but markedly reduced the reactivity of animals subjected to noxious chemical or mechanical stimuli. On the other hand, intrathecal administration of BC (3016) significantly attenuated nociception of animals to a thermal stimulus. The in vivo neurobehavioral effects of BC (3016) appear to be kappa selective since the drug did not decrease body temperature, increase muscular tone or induce catalepsy, three effects generally attributed to μ agonists. Furthermore, BC (3016) antagonized the immobility, trunk rigidity, catalepsy and analgesia induced by morphine. In summary, the present results reveal that BC (3016) displays a profile of neurobehavioral effects similar to that of well known kappa agonists.
Robert Rivest - One of the best experts on this subject based on the ideXlab platform.
-
Neurobehavioral evidence for kappa agonist activity of the Morphinan Derivative 14-β-methyl 8-oxacyclorphan [BC (3016)]
Pharmacology biochemistry and behavior, 1991Co-Authors: François B. Jolicoeur, Simon Lemaire, Daniel Ménard, Robert Rivest, Bernard BelleauAbstract:Abstract The purpose of the present study was to determine if the in vivo neurobehavioral effects of the Morphinan 14-β-methyl 8-oxacyclorphan, [BC (3016)], would reflect the kappa agonist activity found in our previous in vitro studies. The effects of intracisternal administration of various doses (10–80 μg) of BC (3016) on body temperature, muscle rigidity, nociception of thermal, chemical and mechanical stimuli as well as its ability to induce catelepsy were examined. The effects of intrathecal administration of the same doses of the compound on reactivity of animals to a thermal stimulus were also assessed. Finally, the ability of BC (3016) to antagonize well known neurobehavioral effects of morphine was investigated. Results indicate that the analgesic properties of BC (3016) resemble those of typical kappa agonists: Intracisternal administration of the drug failed to affect nociception to an aversive thermal stimulus but markedly reduced the reactivity of animals subjected to noxious chemical or mechanical stimuli. On the other hand, intrathecal administration of BC (3016) significantly attenuated nociception of animals to a thermal stimulus. The in vivo neurobehavioral effects of BC (3016) appear to be kappa selective since the drug did not decrease body temperature, increase muscular tone or induce catalepsy, three effects generally attributed to μ agonists. Furthermore, BC (3016) antagonized the immobility, trunk rigidity, catalepsy and analgesia induced by morphine. In summary, the present results reveal that BC (3016) displays a profile of neurobehavioral effects similar to that of well known kappa agonists.