| Description |
DSR-141562 is a novel, orally active, and selective brain-penetrant phosphodiesterase 1 (PDE1) inhibitor. DSR-141562 shows preferential selectivity for human PDE1B with an IC50 of 43.9 nM, and the IC50 values for human PDE1A and 1C are 97.6 and 431.8 nM, respectively. DSR-141562 can be used for the study of positive symptoms, negative symptoms and cognitive impairments associated with schizophrenia[1][2].
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| Related Catalog |
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| Target |
IC50: 43.9 nM (human PDE1B) IC50: 97.6 nM (human PDE1A) IC50: 431.8 nM (human PDE1C)
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| In Vivo |
DSR-141562 (oral administration; 30 mg/kg; single dose; plasma and brain exposures 0.5, 1, 2, and 3 hours after administration) exhibits good brain uptake, with the brain-to-blood concentration ratio of unbound drug being 0.99 in rats. DSR-141562 (oral administration; 10 mg/kg; single dose; 2 hours) slightly but significantly increases cGMP contents in the frontal cortex and striatum in rat[1]. DSR-141562 (oral administration; 30 mg/kg or 100 mg/kg; single dose; 2 hours) causes a significant increase in cGMP concentration in monkey CSF. The plasma concentrations of unbound this compound are above 43.9 nM (IC50s)for PDE1B in vitro (43.9 nM). DSR-141562 causes a significant increase in cGMP concentration in monkey CSF[1]. DSR-141562 (oral administration; 3 mg/kg, 10 mg/kg and 30 mg/kg; single dose) significantly reverses methamphetamine-induced locomotor hyperactivity, but has no effect on spontaneouslocomotor activity at 3 and 10 mg/kg[1]. DSR-141562 (oral administration; 0.3 mg/kg, 1 mg/kg or 3 mg/kg) significantly reversed the phencyclidine-induced decrease of social interaction time in mice[1]. Animal Model: Male SpragueDawley rats[1] Dosage: 3 mg/kg, 10 mg/kg and 30 mg/kg Administration: Oral administration; single dose Result: Inhibited methamphetamine-induced locomotor hyperactivity in rats, while it had only minimal effects on the spontaneous locomotor activity. Animal Model: Male SpragueDawley rats[1] Dosage: 0.3 mg/kg, 1 mg/kg or 3 mg/kg Administration: Oral administration; single dose Result: Reversed social interaction.
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| References |
[1]. Takeshi Enomoto, et al.A Novel Phosphodiesterase 1 Inhibitor DSR-141562 Exhibits Efficacies in Animal Models for Positive, Negative, and Cognitive Symptoms Associated With Schizophrenia. J Pharmacol Exp Ther [2]. Takeshi Enomoto, et al. The Preclinical Profile of DSR-141562: A Novel Phosphodiesterase 1 Inhibitor for the Treatment of Positive Symptoms, Negative Symptoms and Cognitive Impairments Associated with Schizophrenia.Proceedings for The 93rd Annual Meeting of the Japanese Pharmacological Society
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