Delving into the Latest Updates on Deuterated Paroxetine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

NET x SERT

Mechanism

NET inhibitors(Norepinephrine transporter inhibitors), Serotonin reuptake inhibitors

Therapeutic Areas

Nervous System DiseasesOtorhinolaryngologic DiseasesOther Diseases

Active Indication-

Inactive Indication

Hot FlashesPainTinnitus

Originator Organization

Concert Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Concert Pharmaceuticals, Inc.

Syntrix Biosystems, Inc.

GSK Plc

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H20FNO3

InChIKeyAHOUBRCZNHFOSL-SVLNYFRSSA-N

CAS Registry923932-43-8

Selective deuterium substitution as a means of ameliorating clinically relevant pharmacokinetic drug interactions is demonstrated in this study. Carbon-deuterium bonds are more stable than corresponding carbon-hydrogen bonds. Using a precision deuteration platform, the two hydrogen atoms at the methylenedioxy carbon of paroxetine were substituted with deuterium. The new chemical entity, CTP-347 [(3S,4R)-3-((2,2-dideuterobenzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine], demonstrated similar selectivity for the serotonin receptor, as well as similar neurotransmitter uptake inhibition in an in vitro rat synaptosome model, as unmodified paroxetine. However, human liver microsomes cleared CTP-347 faster than paroxetine as a result of decreased inactivation of CYP2D6. In phase 1 studies, CTP-347 was metabolized more rapidly in humans and exhibited a lower pharmacokinetic accumulation index than paroxetine. These alterations in the metabolism profile resulted in significantly reduced drug-drug interactions between CTP-347 and two other CYP2D6-metabolized drugs: tamoxifen (in vitro) and dextromethorphan (in humans). Our results show that precision deuteration can improve the metabolism profiles of existing pharmacotherapies without affecting their intrinsic pharmacologies.

100 Deals associated with Deuterated Paroxetine

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