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Mark J Millan - One of the best experts on this subject based on the ideXlab platform.

  • discriminative stimulus properties of s32504 a novel d3 d2 receptor agonist and Antiparkinson Agent in rats attenuation by the antipsychotics aripiprazole bifeprunox n desmethylclozapine and by selective antagonists at dopamine d2 but not d3 receptor
    Psychopharmacology, 2007
    Co-Authors: Mark J Millan, Loretta Iob, Jeanlouis Peglion, Anne Dekeyne
    Abstract:

    Rationale Drug-discrimination studies have proven instructive in the characterization of psychotropic Agents, a procedure applied herein to the novel Antiparkinson Agent, S32504. This highly selective agonist at dopamine D3 and (less potently) D2 receptors displays potent Antiparkinson, neuroprotective and antidepressant properties (Millan et al., J Pharmacol Exp Ther 309:936–950, 2004a; Millan et al., J Pharmacol Exp Ther 309:903–920, 2004b; Millan et al., J Pharmacol Exp Ther 309:921–935, 2004c).

  • neuroprotective effects of the novel d3 d2 receptor agonist and Antiparkinson Agent s32504 in vitro against 1 methyl 4 phenylpyridinium mpp and in vivo against 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine mptp a comparison to ropinirole
    Experimental Neurology, 2003
    Co-Authors: Jeffrey N Joyce, Steve Presgraves, Lynn Renish, Sabinne Borwege, Tracy Osredkar, Diane Hagner, Maria Replogle, Mateo Pazsoldan, Mark J Millan
    Abstract:

    Abstract The novel naphtoxazine derivative and preferential D3 vs D2 receptor agonist, S32504, restores perturbed motor function in rodent and primate models of Antiparkinsonian activity with a potency superior to those of two further, preferential D3 receptor agonists, pramipexole and ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SY5Y cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP+ and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of Antiparkinson activity.

Mark Millan - One of the best experts on this subject based on the ideXlab platform.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of α2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, Mark Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of acetylcholinesterase inhibitors to “boost” basal levels of acetylcholine (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other Antiparkinson drugs and selective ligands at α2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of α2A-ARs upon cholinergic transmission, the α2-AR agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the preferential α2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzodioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential α2A-AR antagonist 2-(2 H -(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). In contrast, trans -2,3,9,13 b -tetrahydro-1,2-dimethyl-1 H -dibenz[ c , f ]imidazo[1,5-a]azepine (BRL41992) and prazosin, preferential α2B/2C-AR antagonists, were inactive. The dopaminergic agonist and Antiparkinson Agent piribedil, which behaves as an antagonist at α2-ARs, dose dependently increased extracellular levels of ACh. This action was absent upon pretreatment with a maximally effective dose of RX821002. On the other hand, a further dopaminergic agonist and Antiparkinson Agent, talipexole, which possesses agonist properties at α2-ARs, dose dependently reduced levels of ACh. This action was also blocked by RX821002. In contrast to piribedil and talipexole, quinelorane, which interacts with dopaminergic receptors but not α2-ARs, failed to affect ACh levels. Finally, in analogy to the frontal cortex, piribedil likewise elicited a dose-dependent increase in extracellular levels of ACh in the dorsal hippocampus. In conclusion, in distinction to talipexole and quinelorane, and reflecting its antagonist properties at α2A-ARs, piribedil reinforces cholinergic transmission in the frontal cortex and dorsal hippocampus of freely moving rats. These actions may be related to its facilitatory influence upon cognitive function.

Alain Gobert - One of the best experts on this subject based on the ideXlab platform.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of α2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, Mark Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of acetylcholinesterase inhibitors to “boost” basal levels of acetylcholine (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other Antiparkinson drugs and selective ligands at α2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of α2A-ARs upon cholinergic transmission, the α2-AR agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the preferential α2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzodioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential α2A-AR antagonist 2-(2 H -(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). In contrast, trans -2,3,9,13 b -tetrahydro-1,2-dimethyl-1 H -dibenz[ c , f ]imidazo[1,5-a]azepine (BRL41992) and prazosin, preferential α2B/2C-AR antagonists, were inactive. The dopaminergic agonist and Antiparkinson Agent piribedil, which behaves as an antagonist at α2-ARs, dose dependently increased extracellular levels of ACh. This action was absent upon pretreatment with a maximally effective dose of RX821002. On the other hand, a further dopaminergic agonist and Antiparkinson Agent, talipexole, which possesses agonist properties at α2-ARs, dose dependently reduced levels of ACh. This action was also blocked by RX821002. In contrast to piribedil and talipexole, quinelorane, which interacts with dopaminergic receptors but not α2-ARs, failed to affect ACh levels. Finally, in analogy to the frontal cortex, piribedil likewise elicited a dose-dependent increase in extracellular levels of ACh in the dorsal hippocampus. In conclusion, in distinction to talipexole and quinelorane, and reflecting its antagonist properties at α2A-ARs, piribedil reinforces cholinergic transmission in the frontal cortex and dorsal hippocampus of freely moving rats. These actions may be related to its facilitatory influence upon cognitive function.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of 2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    2002
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, M. J. Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of ace-tylcholinesterase inhibitors to “boost ” basal levels of acetylcho-line (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other antipar-kinson drugs and selective ligands at 2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of 2A-ARs upon cho-linergic transmission, the 2-AR agonist 5-bromo-6-[2-imida-zolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the pref-erential 2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzo-dioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential 2A-AR antagonist 2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). I

B. Di Cara - One of the best experts on this subject based on the ideXlab platform.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of α2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, Mark Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of acetylcholinesterase inhibitors to “boost” basal levels of acetylcholine (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other Antiparkinson drugs and selective ligands at α2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of α2A-ARs upon cholinergic transmission, the α2-AR agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the preferential α2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzodioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential α2A-AR antagonist 2-(2 H -(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). In contrast, trans -2,3,9,13 b -tetrahydro-1,2-dimethyl-1 H -dibenz[ c , f ]imidazo[1,5-a]azepine (BRL41992) and prazosin, preferential α2B/2C-AR antagonists, were inactive. The dopaminergic agonist and Antiparkinson Agent piribedil, which behaves as an antagonist at α2-ARs, dose dependently increased extracellular levels of ACh. This action was absent upon pretreatment with a maximally effective dose of RX821002. On the other hand, a further dopaminergic agonist and Antiparkinson Agent, talipexole, which possesses agonist properties at α2-ARs, dose dependently reduced levels of ACh. This action was also blocked by RX821002. In contrast to piribedil and talipexole, quinelorane, which interacts with dopaminergic receptors but not α2-ARs, failed to affect ACh levels. Finally, in analogy to the frontal cortex, piribedil likewise elicited a dose-dependent increase in extracellular levels of ACh in the dorsal hippocampus. In conclusion, in distinction to talipexole and quinelorane, and reflecting its antagonist properties at α2A-ARs, piribedil reinforces cholinergic transmission in the frontal cortex and dorsal hippocampus of freely moving rats. These actions may be related to its facilitatory influence upon cognitive function.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of 2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    2002
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, M. J. Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of ace-tylcholinesterase inhibitors to “boost ” basal levels of acetylcho-line (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other antipar-kinson drugs and selective ligands at 2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of 2A-ARs upon cho-linergic transmission, the 2-AR agonist 5-bromo-6-[2-imida-zolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the pref-erential 2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzo-dioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential 2A-AR antagonist 2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). I

Laetitia Cistarelli - One of the best experts on this subject based on the ideXlab platform.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of α2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, Mark Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of acetylcholinesterase inhibitors to “boost” basal levels of acetylcholine (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other Antiparkinson drugs and selective ligands at α2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of α2A-ARs upon cholinergic transmission, the α2-AR agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the preferential α2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzodioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential α2A-AR antagonist 2-(2 H -(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). In contrast, trans -2,3,9,13 b -tetrahydro-1,2-dimethyl-1 H -dibenz[ c , f ]imidazo[1,5-a]azepine (BRL41992) and prazosin, preferential α2B/2C-AR antagonists, were inactive. The dopaminergic agonist and Antiparkinson Agent piribedil, which behaves as an antagonist at α2-ARs, dose dependently increased extracellular levels of ACh. This action was absent upon pretreatment with a maximally effective dose of RX821002. On the other hand, a further dopaminergic agonist and Antiparkinson Agent, talipexole, which possesses agonist properties at α2-ARs, dose dependently reduced levels of ACh. This action was also blocked by RX821002. In contrast to piribedil and talipexole, quinelorane, which interacts with dopaminergic receptors but not α2-ARs, failed to affect ACh levels. Finally, in analogy to the frontal cortex, piribedil likewise elicited a dose-dependent increase in extracellular levels of ACh in the dorsal hippocampus. In conclusion, in distinction to talipexole and quinelorane, and reflecting its antagonist properties at α2A-ARs, piribedil reinforces cholinergic transmission in the frontal cortex and dorsal hippocampus of freely moving rats. These actions may be related to its facilitatory influence upon cognitive function.

  • Piribedil Enhances Frontocortical and Hippocampal Release of Acetylcholine in Freely Moving Rats by Blockade of 2A-Adrenoceptors: A Dialysis Comparison to Talipexole and Quinelorane in the Absence of Acetylcholinesterase Inhibitors
    2002
    Co-Authors: Alain Gobert, B. Di Cara, Laetitia Cistarelli, M. J. Millan
    Abstract:

    In a dialysis procedure not requiring perfusate addition of ace-tylcholinesterase inhibitors to “boost ” basal levels of acetylcho-line (ACh), the influence of the Antiparkinson Agent piribedil upon levels of ACh in frontal cortex and dorsal hippocampus of freely moving rats was compared with those of other antipar-kinson drugs and selective ligands at 2-adrenoceptors (ARs). Suggesting a tonic, inhibitory influence of 2A-ARs upon cho-linergic transmission, the 2-AR agonist 5-bromo-6-[2-imida-zolin-2-yl-amino]-quinoxaline tartrate (UK14,304), and the pref-erential 2A-AR agonist guanabenz reduced levels of ACh. They were elevated by the antagonists 2(2-methoxy-1,4 benzo-dioxan-2-yl)-2-imidazoline HCl (RX821002) and atipamezole and by the preferential 2A-AR antagonist 2-(2H-(1-methyl-1,3-dihydroisoindole)methyl)-4,5-dihydroimidazole (BRL44008). I