The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Kazuo Hanaoka - One of the best experts on this subject based on the ideXlab platform.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European journal of pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European Journal of Pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Abstract Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2β: analog 1, 2α: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED50s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
Mark L Trudell - One of the best experts on this subject based on the ideXlab platform.
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Regioselective synthesis and cannabinoid Receptor Binding Affinity of N-alkylated 4,5-diaryl-1,2,3-triazoles
Medicinal Chemistry Research, 2012Co-Authors: Murali Papudippu, Sari Izenwasser, Dean Wade, Gerard Gulasey, Steven Fournet, Edwin D. Stevens, Stacey A. Lomenzo, Mark L TrudellAbstract:A series of N1- and N2-substituted 4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1,2,3-triazoles were regioselectively synthesized to explore the Binding motifs of the diaryl-1,2,3-triazole scaffold at CB1 Receptors. The N1 analogs were regioselectively constructed via Click chemistry to furnish analogs with modest CB1 Receptor Affinity ( K _i
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European journal of pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European Journal of Pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Abstract Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2β: analog 1, 2α: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED50s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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synthesis of optically pure epibatidine analogs 1r 2r 5s 2β 2 chloro 5 pyridinyl 8 azabicyclo 3 2 1 octane and 1r 2s 5s 2α 2 chloro 5 pyridinyl 8 azabicyclo 3 2 1 octane from cocaine
Tetrahedron Letters, 1997Co-Authors: Chunming Zhang, Laszlo Gyermek, Mark L TrudellAbstract:Abstract Two optically pure epibatidine analogs, 4 and 5 , which contain the 8-azabicyclo[3.2.1]octane ring system were synthesized from (−)-cocaine. The nicotinic Receptor Binding Affinity and the stimulant activity of 4 and 5 were measured to be significantly lower than racemic epibatidine (± -1 ).
Tomoki Nishiyama - One of the best experts on this subject based on the ideXlab platform.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European journal of pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European Journal of Pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Abstract Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2β: analog 1, 2α: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED50s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
Laszlo Gyermek - One of the best experts on this subject based on the ideXlab platform.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European journal of pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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Spinally mediated analgesia and Receptor Binding Affinity of epibatidine analogs.
European Journal of Pharmacology, 2003Co-Authors: Tomoki Nishiyama, Laszlo Gyermek, Mark L Trudell, Kazuo HanaokaAbstract:Abstract Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2β: analog 1, 2α: analog 2, were investigated for their spinally mediated analgesic effects and Binding Affinity to nicotinic acetylcholine Receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand Binding utilizing [3H] epibatidine displacement. Their Affinity to muscular and neuronal nicotinic acetylcholine Receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED50s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.
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synthesis of optically pure epibatidine analogs 1r 2r 5s 2β 2 chloro 5 pyridinyl 8 azabicyclo 3 2 1 octane and 1r 2s 5s 2α 2 chloro 5 pyridinyl 8 azabicyclo 3 2 1 octane from cocaine
Tetrahedron Letters, 1997Co-Authors: Chunming Zhang, Laszlo Gyermek, Mark L TrudellAbstract:Abstract Two optically pure epibatidine analogs, 4 and 5 , which contain the 8-azabicyclo[3.2.1]octane ring system were synthesized from (−)-cocaine. The nicotinic Receptor Binding Affinity and the stimulant activity of 4 and 5 were measured to be significantly lower than racemic epibatidine (± -1 ).
A. Michael Crider - One of the best experts on this subject based on the ideXlab platform.
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cis- and trans-2,3,3a,4,5,9b-Hexahydro-1H-benz[e]indoles: synthesis and evaluation of dopamine D2, and D3 Receptor Binding Affinity
European Journal of Medicinal Chemistry, 1999Co-Authors: Xiaodong Song, A. Michael Crider, Sharon F. Cruse, Debasis Ghosh, Cheryl Klein-stevens, Li Liang, Mark A. Scheideler, Annemarie Reinhardt Varming, Inger SøtofteAbstract:Abstract cis- and trans-2,3,3a,4,5,9b-Hexahydro-1H-benz[e]indoles were synthesized as conformationally rigid analogues of 3-phenylpyrrolidine and evaluated for dopamine (DA) D2S and D3 Receptor Binding Affinity. The tricyclic benz[e]indole nucleus was constructed by a previously reported reductive amination-cyclization procedure. Several unexpected side products were isolated and characterized using the general method. The trans-diastereoisomers exhibited greater affinities for the DA D3 Receptor than the corresponding cis-isomers. In both the cis- and trans- series the greatest Affinity for DA D3 Receptors was shown by compounds substituted with N-n-propyl or N-allyl groups. The cis-(±)-N-allyl derivative 21e demonstrated a D2S/D3 selectivity of 290. Resolution of cis-(±)-5 and trans-(±)-21c into individual enantiomers showed that in both series the more active isomer had 3aR absolute configuration. These novel ligands may be useful tools for gaining additional information about the DA D3 Receptor.
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Synthesis and evaluation of cis-1-methyl-3-n-propyl-2,3,3a,4,5,9b-hexahydro-1H-benz[e]indoles for in vitro dopamine D1 and D2 Receptor Binding Affinity
European Journal of Medicinal Chemistry, 1995Co-Authors: Debasis Ghosh, C. L. Klein, B. Garner, Peter H. Andersen, A. Michael CriderAbstract:Summary cis-syn-1-Methyl-3-n-propyl-2,3,3a,4,5,9b-hexahydro-1H-benz[e]indoles 6 and 7 were synthesized as conformationally rigid analogs of 4-methyl-3-(3,4-dihydroxyphenyl)-1-(n-propyl)pyrrolidine 1 and evaluated for dopamine D1 and D2 Receptor Binding Affinity. The target compounds 6 and 7 were obtained from the key tricyclic lactams 10 and 11, respectively. The stereochemistry was confirmed by single crystal X-ray analysis. Compounds 6 and 7 demonstrated low in vitro Binding Affinity at D1 and D2 Receptors using [3H]SCH 23390 and [3H]spiperone as the D1 and D2 Receptor radioligands, respectively. These data suggest that the 1-methyl group may interfere with the Binding of 6 and 7 at D1 and D2 Receptors. Molecular modeling studies revealed that unlike the 4-methyl group of 1, the 1-methyl group of 6 and 7 was directed toward the so-called ‘steric occlusion site’ of the dopamine Receptor.
