Delving into the Latest Updates on Cerlapirdine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cerlapirdine

+ [2]

Target

5-HT6 receptor

Mechanism

5-HT6 receptor antagonists(Serotonin 6 (5-HT6) receptor antagonists)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Alzheimer Disease

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Wyeth AB

Pfizer Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H24ClN3O3S

InChIKeyRNGAZJUESDPASQ-UHFFFAOYSA-N

CAS Registry925447-04-7

The objective of this study is to investigate how quickly and to what extent the 14-Carbon labeled SAM-531 is absorbed into the bloodstream, converted and eliminated from the body after oral administration in healthy male subjects. As 14-Carbon labeled SAM-531 is radioactive, this enables the compound to be traced in blood, urine and feces.

Start Date01 May 2009

Sponsor / Collaborator

Wyeth AB

100 Clinical Results associated with Cerlapirdine Hydrochloride

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100 Translational Medicine associated with Cerlapirdine Hydrochloride

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100 Patents (Medical) associated with Cerlapirdine Hydrochloride

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4

Literatures (Medical) associated with Cerlapirdine Hydrochloride

26 Jun 2023·Angewandte Chemie

Exploring Synthetic Strategies for 1H‐Indazoles and Their N‐Oxides: Electrochemical Synthesis of 1H‐Indazole N‐Oxides and Their Divergent C−H Functionalizations

Article

Author: Kim, Gyeongho ; Arepally, Sagar ; Park, Jin Kyoon ; Kim, Taehoon ; Yang, Haesik

AbstractThe selective electrochemical synthesis of 1H‐indazoles and their N‐oxides and the subsequent C−H functionalization of the 1H‐indazole N‐oxides are described. The electrochemical outcomes were determined by the nature of the cathode material. When a reticulated vitreous carbon cathode was used, a wide range of 1H‐indazole N‐oxides were selectively synthesized, and the electrosynthesis products were deoxygenated to N‐heteroaromatics, owing to cathodic cleavage of the N−O bond via paired electrolysis, when a Zn cathode was used. The scope of this electrochemical protocol is broad, as both electron‐rich and electron‐poor substrates were tolerated. The potency of this electrochemical strategy was demonstrated through the late‐stage functionalization of various bioactive molecules, making this reaction attractive for the synthesis of 1H‐indazole derivatives for pharmaceutical research and development. Detailed mechanistic investigations involving electron paramagnetic resonance spectroscopy and cyclic voltammetry suggested a radical pathway featuring iminoxyl radicals. Owing to the rich reactivity of 1H‐indazole N‐oxides, diverse C−H functionalization reactions were performed. We demonstrated the synthetic utility of 1H‐indazole N‐oxides by synthesizing the pharmaceutical molecules lificiguat and YD (3); key intermediates for bendazac, benzydamine, norepinephrine/serotonin reuptake inhibitors, SAM‐531, and gamendazole analogues; and a precursor for organic light‐emitting diodes.

01 Dec 2014·Drug Metabolism and DispositionQ2 · MEDICINE

Disposition and Metabolic Profiling of [14C]Cerlapirdine Using Accelerator Mass Spectrometry

Q2 · MEDICINE

Article

Author: Tse, Susanna ; Leung, Louis ; Shishikura, Yoko ; Raje, Sangeeta ; Seymour, Mark ; Obach, R Scott

Cerlapirdine (SAM-531, PF-05212365) is a selective, potent, full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine and other 5-HT6 receptor antagonists have been in clinical development for the symptomatic treatment of Alzheimer's disease. A human absorption, distribution, metabolism, and excretion study was conducted to gain further understanding of the metabolism and disposition of cerlapirdine. Because of the low amount of radioactivity administered, total (14)C content and metabolic profiles in plasma, urine, and feces were determined using accelerator mass spectrometry (AMS). After a single, oral 5-mg dose of [(14)C]cerlapirdine (177 nCi), recovery of total (14)C was almost complete, with feces being the major route of elimination of the administered dose, whereas urinary excretion played a lesser role. The extent of absorption was estimated to be at least 70%. Metabolite profiling in pooled plasma samples showed that unchanged cerlapirdine was the major drug-related component in circulation, representing 51% of total (14)C exposure in plasma. One metabolite (M1, desmethylcerlapirdine) was detected in plasma, and represented 9% of the total (14)C exposure. In vitro cytochrome P450 reaction phenotyping studies showed that M1 was formed primarily by CYP2C8 and CYP3A4. In pooled urine samples, three major drug-related peaks were detected, corresponding to cerlapirdine-N-oxide (M3), cerlapirdine, and desmethylcerlapirdine. In feces, cerlapirdine was the major (14)C component excreted, followed by desmethylcerlapirdine. The results of this study demonstrate that the use of the AMS technique enables comprehensive quantitative elucidation of the disposition and metabolic profiles of compounds administered at a low radioactive dose.

16 Jan 2013·ACS Chemical NeuroscienceQ3 · MEDICINE

Activation of 5-HT6 Receptors Modulates Sleep–Wake Activity and Hippocampal Theta Oscillation

Q3 · MEDICINE

Article

Author: Pishdari, Bano ; Lok, Ling Ling ; Hajos, Mihaly ; Ly, Susanna ; Kocsis, Bernat

The modulatory role of 5-HT neurons and a number of different 5-HT receptor subtypes has been well documented in the regulation of sleep-wake cycles and hippocampal activity. A high level of 5-HT(6) receptor expression is present in the rat hippocampus. Further, hippocampal function has been shown to be modulated by both 5-HT(6) agonists and antagonists. In the current study, the potential involvement of 5-HT(6) receptors in the control of hippocampal theta rhythms and sleep-wake cycles has been investigated. Hippocampal activity was recorded by intracranial hippocampal electrodes both in anesthetized (n = 22) and in freely moving rats (n = 9). Theta rhythm was monitored in different sleep-wake states in freely moving rats and was elicited by stimulation of the brainstem reticular formation under anesthesia. Changes in theta frequency and power were analyzed before and after injection of the 5-HT(6) antagonist (SAM-531) and the 5-HT(6) agonist (EMD386088). In freely moving rats, EMD386088 suppressed sleep for several hours and significantly decreased theta peak frequency, while, in anesthetized rats, EMD386088 had no effect on theta power but significantly decreased theta frequency, which could be blocked by coadministration of SAM-531. SAM-531 alone did not change sleep-wake patterns and had no effect on theta parameters in both unanesthetized and anesthetized rats. Decreases in theta frequency induced by the 5-HT(6) receptor agonist correspond to previously described electrophysiological patterns shared by all anxiolytic drugs, and it is in line with its behavioral anxiolytic profile. The 5-HT(6) antagonist, however, failed to potentiate theta power, which is characteristic of many pro-cognitive substances, indicating that 5-HT(6) receptors might not tonically modulate hippocampal oscillations and sleep-wake patterns.

100 Deals associated with Cerlapirdine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Cerlapirdine Hydrochloride	-	DB12229

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	ZA	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	JP	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	JP	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	NZ	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	NZ	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	ZA	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	KR	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	CO	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	CO	Pfizer Inc.	01 May 2009
Alzheimer Disease	Phase 2	KR	Pfizer Inc.	01 May 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAIC2010	Not Applicable	Alzheimer Disease	74	SAM-531 1.5 mg	utychnrmxw(jyntwnxwzs) = cuxlqgedet wxuljtbitr (saneletyua )	-	01 Jul 2010
				SAM-531 3.0 mg	utychnrmxw(jyntwnxwzs) = jkihjjczox wxuljtbitr (saneletyua )