Delving into the Latest Updates on Landipirdine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Landipirdine (USAN/INN)

+ [5]

Target

5-HT2A receptor x 5-HT6 receptor

Mechanism

5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), 5-HT6 receptor antagonists(Serotonin 6 (5-HT6) receptor antagonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication

Cognition DisordersDementia due to Parkinson's disease

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization

F. Hoffmann-La Roche Ltd.

Inactive Organization

Acorda Therapeutics, Inc.Biotie Therapies Oy

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC18H19FN2O3S

InChIKeyMTTHRRVVGMPYQG-ZDUSSCGKSA-N

CAS Registry1000308-25-7

BACKGROUNDSYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms.OBJECTIVESWe evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD).METHODSIn a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI).RESULTSEighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028).CONCLUSIONSSYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study.REGISTRATIONClinicaltrials.gov as NCT02258152.

17 May 2017·ACS Chemical NeuroscienceQ3 · MEDICINE

Serotonergic Approaches in Parkinson’s Disease: Translational Perspectives, an Update

Q3 · MEDICINE

Review

Author: Fox, Susan H. ; Huot, Philippe ; Sgambato-Faure, Véronique ; McCreary, Andrew C.

Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model of PD that presents with dual dopamine and 5-HT lesions. We then present preclinical and clinical data that introduce new concepts, such as the use of biased and partial agonists, as well as molecules recently introduced to the field of PD, such as eltoprazine, pimavanserin, nelotanserin, and SYN-120, to enhance therapeutic benefit while minimizing adverse events, notably on parkinsonian disability.

Neuropsychiatric Disease and TreatmentQ4 · MEDICINE

<p>Serotonin Type 6 and 7 Receptors as a Novel Therapeutic Target for the Treatment of Schizophrenia</p>

Q4 · MEDICINE

ReviewOA

Author: Tsegay, Etsay Weldekidan ; Gufue, Zenawi Hagos ; Hailu, Nigus Alemu ; Demise, Desalegn Getnet

Schizophrenia is a serious disease of the central nervous system that affects a person's ability to think, feel and behave clearly. Even though the pathophysiological hypothesis of the disease is not clearly understood, dysfunction of dopamine, glutamate, serotonin and other neurotransmitters is widely believed to be involved. Serotonin within the synaptic vesicles functions as neurotransmitter and neurohormone in regulation of emotion, learning, memory, hormone release, cognition and motor function. Dysfunction of normal brain activity of serotonin is associated with schizophrenia. The role of serotonin 6 and 7 receptors in schizophrenia, interaction with neurotransmitters and the effect of drugs on those receptors in schizophrenia are the goal of this review. The aim of this review was to provide information for researchers and other scholars to identify the possible intervention points in the management of schizophrenia. The serotonin 6 and 7 receptors are associated with schizophrenia via modulating cyclic adenosine monophosphate, regulation of Fyn kinase and induction of structural plasticity. The above modulatory effects affect cholinergic, dopaminergic, glutamatergic, adrenergic and GABAergic systems. Recently, diverse numbers of selective agonist and antagonist ligands were developed for both receptors. SGS-518, ABT-354, Lu AE58054, SB-742,457, S-518, AVN-211, AVN-322, SYN-114 and SYN-120 are serotonin 6 receptor antagonists and aripiprazole-controlled release serotonin 7 receptor agonists under clinical trial for schizophrenia. Thus, research on novel drugs that act on serotonin 6 and 7 receptors likely facilitates the intervention into schizophrenia patients seeking better quality of life in the future.

100 Deals associated with Landipirdine

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External Link

KEGG	Wiki	ATC	Drug Bank
D11157	-	-	DB16214

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 2	-	F. Hoffmann-La Roche Ltd.	-
Dementia due to Parkinson's disease	Phase 1	US	Acorda Therapeutics, Inc.	22 Dec 2014
Cognition Disorders	Preclinical	US	Biotie Therapies Oy	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02258152 (SYNAPSE, CTgov)	Phase 2	Dementia due to Parkinson's disease	82	Placebo (Placebo)	tgyvtffozg(qnmubqrsgs) = poxasnised lynnngjsfz (noylgghxmg, kujcfzaikh - dxetmcnsge) View more	-	19 Apr 2019
				SYN120 (SYN120)	tgyvtffozg(qnmubqrsgs) = kcmkojwbyz lynnngjsfz (noylgghxmg, lepcroohhg - klaqmdaeyd) View more
MDS2018	Phase 2	Progressive Supranuclear Palsy Atypical	-	SYN120 100 mg daily	blrsqdqsbc(yitocpmqkf) = Numerical improvements with SYN120 compared to placebo were also noted for SCOPA-SLEEP nighttime sleep (ES=0.47; p=0.05) higvcnurvv (piksggzoqr ) View more	-	05 Oct 2018
				Placebo
NCT02258152 (SYNAPSE, MDS2018)	Phase 2	Progressive Supranuclear Palsy Atypical	82	SYN120 100 mg daily	stdwwnfrkf(ybcodowvon) = incidence of nausea and vomiting were two-fold higher with SYN120 lzmrgpwfkc (xhsjqlfzzw ) View more	Negative	05 Oct 2018
				Placebo