Pharmacological and Behavioral Profile of N-(4-Fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) Carbamide (2R,3R)-Dihydroxybutanedioate (2:1) (ACP-103), a Novel 5-Hydroxytryptamine2A Receptor Inverse Agonist
@article{Vanover2006PharmacologicalAB, title={Pharmacological and Behavioral Profile of N-(4-Fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) Carbamide (2R,3R)-Dihydroxybutanedioate (2:1) (ACP-103), a Novel 5-Hydroxytryptamine2A Receptor Inverse Agonist}, author={Kimberly E. Vanover and David M Weiner and Malath M. Makhay and Isaac Veinbergs and Luis R. Gardell and Jelveh Lameh and Andria L Del Tredici and Fabrice Piu and Hans H. Schiffer and Thomas R. Ott and Ethan S. Burstein and Allan K. Uldam and Mikkel Boas Thygesen and Nathalie Schlienger and Carl Magnus Andersson and Thomas Son and Scott C. Harvey and Susan B. Powell and Mark A. Geyer and Bo Tolf and Mark R. Brann and Robert E Davis}, journal={Journal of Pharmacology and Experimental Therapeutics}, year={2006}, volume={317}, pages={910 - 918} }
The in vitro and in vivo pharmacological properties of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103) are presented. A potent 5-hydroxytryptamine (5-HT)2A receptor inverse agonist ACP-103 competitively antagonized the binding of [3H]ketanserin to heterologously expressed human 5-HT2A receptors with a mean pKi of 9.3 in membranes and 9.70 in whole cells. ACP-103 displayed potent inverse agonist…
154 Citations
A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model
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Using ACP-103 as an adjunctive therapy to currently used APDs may result in enhanced antipsychotic efficacy while reducing adverse effects including those attributable to D2 receptor antagonism.
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Subchronic administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP), in rodents has been shown to produce impairment in novel object recognition (NOR), a model of visual…
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All doses of nelotanserin significantly improved measures of sleep consolidation, including decreases in the number of stage shifts, number of awakenings after sleep onset, microarousal index, and number of sleep bouts, concomitant with increases in sleep bout duration.
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- Medicine, BiologyJournal of clinical pharmacology
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The effects of food on the pharmacokinetics of ACP-103 after a single oral administration were evaluated in healthy male subjects and the results were compared to those after administration of the solution of ACp-103.
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Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats
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The results indicate that mGlu2/3 agonism can potentiate the ability of atypical, but not typical APDs, to ameliorate the effect of subchronic PCP on NOR, and suggest thatmGlu 2/3 receptor agonism should be investigated as an adjunctive treatment of cognitive impairment in schizophrenia rather than as monotherapy.
Combined serotonin (5-HT)1A agonism, 5-HT2A and dopamine D2 receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats
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