The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Brigitte Olympe Depelchin - One of the best experts on this subject based on the ideXlab platform.
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advantageous safety profile of a dual selective alpha 2c agonist alpha 2a antagonist Antinociceptive Agent
Fundamental & Clinical Pharmacology, 2014Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
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Advantageous safety profile of a dual selective alpha(2C) agonist/alpha(2A) antagonist Antinociceptive Agent.
Fundamental & Clinical Pharmacology, 2013Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
Annie Delaunois - One of the best experts on this subject based on the ideXlab platform.
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advantageous safety profile of a dual selective alpha 2c agonist alpha 2a antagonist Antinociceptive Agent
Fundamental & Clinical Pharmacology, 2014Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
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Advantageous safety profile of a dual selective alpha(2C) agonist/alpha(2A) antagonist Antinociceptive Agent.
Fundamental & Clinical Pharmacology, 2013Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
F Porreca - One of the best experts on this subject based on the ideXlab platform.
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novel met enkephalin analogue a potent systemic mu agonist Antinociceptive Agent
Pharmacological Research, 1995Co-Authors: Chandishwar Nath, G K Patnaikt, W Haqt, K B Mathur, R C Srimal, B N Dhawan, F PorrecaAbstract:Abstract A new met-enkephalin analogue (compound 82/205) was evaluated for its opioidergic activity in mice. The compound showed antinociception (warm water tail-flick test), tolerance, cross tolerance to morphine and physical dependence. The time course of antinociptive effect of the compound was comparable to morphine. The Antinociceptive ED 50 (μmol kg −1 i.p.) values for the compound and morphine base were 5.31 and 7.59, respectively. Its Antinociceptive effect was blocked by naloxone, β-FNA (mu antagonist) and naloxonazine (mu 1 antagonist) but not by ICI 174,864 (delta antagonist). Naloxone precipitated withdrawal jumpings were 2.6 times less in compound 82/205 treated mice than the morphine treated group. The new analogue compound 82/205 is a potent mu agonist Antinociceptive with a possible weak dependence liability.
Dominique P Bridon - One of the best experts on this subject based on the ideXlab platform.
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site specific 1 1 opioid albumin conjugate with in vitro activity and long in vivo duration
Bioconjugate Chemistry, 2000Co-Authors: Darren L Holmes, Karen Thibaudeau, Benoit Larcheveque, Peter G Milner, And Alan M Ezrin, Dominique P BridonAbstract:: A site-specific 1:1 dynorphin A-(1-13)-NH(2) derivative conjugated specifically to Cys 34 on human serum albumin (CCI-1035) was shown to be an opioid receptor agonist in vitro and to be a long lasting Antinociceptive Agent when administered intravenously to mice as assessed by an acetic acid writhing assay. When 10 micromol/kg of CCI-1035 was administered to mice, rapid antinociception was observed within 5 min following intravenous bolus injection and was sustained beyond 8 h. Antinociceptive activity was absent in a heat induced pain model using a mouse tail-flick assay. This finding represents the first report of a 1:1 albumin opioid conjugate retaining potent in vivo activity equal to or greater than dynorphin A, accompanied by a dramatic extension in duration of action. This novel site-specific bioconjugation technology produces an Agent that may be useful for peripheral pain therapy.
Paul Dedoncker - One of the best experts on this subject based on the ideXlab platform.
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advantageous safety profile of a dual selective alpha 2c agonist alpha 2a antagonist Antinociceptive Agent
Fundamental & Clinical Pharmacology, 2014Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
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Advantageous safety profile of a dual selective alpha(2C) agonist/alpha(2A) antagonist Antinociceptive Agent.
Fundamental & Clinical Pharmacology, 2013Co-Authors: Annie Delaunois, Paul Dedoncker, Marieluce Rosseels, Miranda Cornet, Eric Jnoff, Etienne Hanon, Michel Guyaux, Brigitte Olympe DepelchinAbstract:: A selective α2C -adrenoceptor (AR) agonist was developed for the treatment of neuropathic pain. The objective was to dissociate analgesic activity from cardiovascular and sedative side effects commonly observed with nonselective Agents. A 2-amino-oxazoline derivative (compound A), identified as a dual α2C -AR agonist/α2A -AR antagonist in in vitro-binding assays, exhibited in vivo efficacy in rodent pain models. Its safety profile was compared with that of clonidine in six different in vivo models. Contrary to clonidine, compound A did not induce hypotension in pentobarbital-anesthetized rats, in conscious spontaneous hypertensive rats, or in telemetered dogs. Both Agents induced similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized pithed rats, clonidine showed dose-dependent hypertension and inhibited electrical nerve stimulation-induced tachycardia at doses close to its efficacious doses in the mouse formalin test, while compound A had much weaker vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no sedation was observed with compound A at 30-fold its ED50 in the mouse formalin test, while sedative effects of clonidine started from three-fold its ED50 . These data confirm the advantageous safety profile of the new dual α2C -AR agonist/α2A -AR antagonist Agent vs. the nonselective agonist clonidine.
