Delving into the Latest Updates on MIN-117 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

5-HT1A receptor x 5-HT2A receptor

Action

antagonists

Mechanism

5-HT1A receptor antagonists(Serotonin 1a (5-HT1a) receptor antagonists), 5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

Depressive Disorder

Inactive Indication

Depressive Disorder, MajorPain

Originator Organization

Mitsubishi Tanabe Pharma Corp.

Active Organization

Mitsubishi Tanabe Pharma Corp.

Inactive Organization

Minerva Neurosciences, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H26Cl3N3O4

InChIKeyHRNDUKHBCUTNAL-FERBBOLQSA-N

CAS Registry310392-93-9

View All Structures (2)

MIN-117C03 is a 6-week, 3-arm, randomized, double-blind, placebo controlled study to investigate the safety and efficacy of MIN-117 in male and female patients with Major Depressive Disorder, aged 18 to 65 years. Approximately 324 patients were to be randomly assigned to 1 of 3 treatment arms, including placebo, 2.5 mg MIN-117, or 5.0 mg MIN-117, in a 2:1:1 ratio.

Start Date30 Mar 2018

Sponsor / Collaborator

Minerva Neurosciences, Inc.

EUCTR2015-000306-18-FI

/ Not yet recruitingPhase 2

A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled Study to Evaluate the Efficacy and Safety of 2 doses of MIN-117 in Adult Subjects with Major Depressive Disorder

Start Date02 Sep 2015

Sponsor / Collaborator

Minerva Neurosciences, Inc.

100 Clinical Results associated with MIN-117

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100 Translational Medicine associated with MIN-117

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100 Patents (Medical) associated with MIN-117

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3

Literatures (Medical) associated with MIN-117

01 Sep 2009·The International Journal of NeuropsychopharmacologyQ2 · MEDICINE

Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter

Q2 · MEDICINE

ArticleOA

Author: Nobuharu Goto ; Kazutoshi Suzuki ; Yasuhiro Kuwahara ; Masayuki Suzuki ; Yasunori Morio ; Jun Maeda ; Jun-ichi Maeda ; Takashi Okauchi ; Takeaki Saijo ; Makoto Higuchi ; Tetsuya Suhara

Visualization of neurotransmission components in living small animals using positron emission tomography (PET) has the potential of contributing to the preclinical development of neuroactive drugs, although it is yet to be examined whether quantitative animal PET data on candidate compounds can be extrapolated to humans. Here, we investigated the comparability of the occupancies of serotonin transporter (5-HTT) by therapeutic agents in rat PET studies with our predetermined data from ex- vivo animal experiments and clinical PET scans. Rats were treated with varying doses of fluvoxamine and a newly developed compound, (2S)-1-[4-(3,4-dichlorophenyl) piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride (Wf-516), and underwent PET scans with [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB), a selective radioligand for in-vivo quantification of 5-HTT. PET images indicated a reduction of [11C]DASB binding to 5-HTT as a function of the doses and/or plasma concentrations of fluvoxamine and Wf-516. The doses of these drugs at half-maximal effect (15.2 mg/kg and 3.1 mg/kg, respectively), determined that using binding potentials for [11C]DASB, were comparable to those estimated by our previous ex-vivo measurements in rats (4.5 mg/kg and 1.1 mg/kg, respectively), as there was only a 3-fold difference between these results. Moreover, the plasma concentration of fluvoxamine needed for 50% occupancy of central 5-HTT (6.1 ng/ml) was almost equivalent to the value determined in human PET studies (4.6 ng/ml). These findings support the view that the conjunctive use of small-animal PET and [11C]DASB facilitates a quantitative comparison of in-development drugs targeting 5-HTT with established inhibitors and a predictive estimation of their plasma concentrations exerting therapeutic effects in humans.

01 Jan 2008·Naunyn-Schmiedeberg's Archives of PharmacologyQ4 · MEDICINE

In vivo electrophysiological assessment of the putative antidepressant Wf-516 in the rat raphe dorsalis, locus coeruleus and hippocampus

Q4 · MEDICINE

Article

Author: Blier, P. ; El Mansari, M.

Wf-516 is a potential novel antidepressant. It has high affinity for serotonin (5-hydroxytryptamine; 5-HT) transporters, 5-HT(1A) and 5-HT(2A) receptors. In the present study, the pharmacologic properties of Wf-516 were thus assessed using in vivo electrophysiology in the rat dorsal raphe nucleus (DRN), locus coeruleus (LC) and hippocampus. Glass microelectrodes were lowered into the DRN, LC or hippocampus, and neurons were recorded and tested using systemic or microiontophoretic injections of drugs. In the DRN, cumulative doses of 0.5 mg/kg of Wf-516 were injected intravenously and total inhibition of 5-HT neurons firing was obtained with 2.8 +/- 0.3 mg/kg. The administration of 1 mg/kg of Wf-516, which by itself did not induce a change in the firing of 5-HT neurons, markedly attenuated the inhibitory effect of the 5-HT(1A) autoreceptor agonist LSD, indicating that Wf-516 is a 5-HT(1A) autoreceptor antagonist. In the LC, 1 mg/kg of Wf-516 dampened the inhibitory effect of the preferential 5-HT(2A) agonist DOI on norepinephrine (NE) neurons, indicating that Wf-516 is also a 5-HT(2A) receptor antagonist. In the hippocampus, cumulative intravenous doses of Wf-516 significantly increased the recovery time of firing activity of CA(3) pyramidal neurons after 5-HT applications, indicating an inhibitory effect on 5-HT reuptake. Unlike the 5-HT(1A) antagonist WAY100635, Wf-516 did not block the inhibitory effect of microiontophoretic application of 5-HT, indicating that this drug is devoid of 5-HT(1A) receptor antagonistic activity in this postsynaptic structure. These properties of WF-516 define the transporter/receptorial profile of an antidepressant with superior effectiveness.

PLoS ONEQ3 · CROSS-FIELD

Presynaptic Selectivity of a Ligand for Serotonin 1A Receptors Revealed by In Vivo PET Assays of Rat Brain

Q3 · CROSS-FIELD

ArticleOA

Author: Nobuharu Goto ; Yasuhiro Kuwahara ; Tetsuya Suhara ; Toshimitsu Fukumura ; Makoto Higuchi ; Masayuki Suzuki ; Yasunori Morio ; Jun Maeda ; Jun-ichi Maeda ; Takashi Okauchi ; Takeaki Saijo

A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

100 Deals associated with MIN-117

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External Link

KEGG	Wiki	ATC	Drug Bank
-	MIN-117	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder	Phase 2	-	Mitsubishi Tanabe Pharma Corp.	-
Pain	Discovery	United States	Minerva Neurosciences, Inc.	14 Nov 2018
Depressive Disorder, Major	Discovery	Finland	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	United States	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	Poland	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	Ukraine	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	Georgia	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	Moldova	Minerva Neurosciences, Inc.	30 Mar 2018
Depressive Disorder, Major	Discovery	Bulgaria	Minerva Neurosciences, Inc.	30 Mar 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03446846 (CTgov)	Phase 2	Depressive Disorder, Major	360	MIN-117 5.0 mg (5.0 mg MIN-117)	eewaymxjez(kltqtmigfd) = ayxjpesysv xwmdxmoizq (oifvvastvk, gldcmzoyqs - cjmzpwzqtl) View more	-	17 Dec 2020
				MIN-117 2.5 mg (2.5 mg MIN-117)	eewaymxjez(kltqtmigfd) = kyhtaktzze xwmdxmoizq (oifvvastvk, gkhblpwdnp - pxjyiibwaj) View more