Delving into the Latest Updates on Lomerizine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Lomerazine, Lomerizine, Lomerizine hydrochloride (JAN)

+ [7]

Target

calcium channel

Mechanism

calcium channel inhibitors(Calcium Channel inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication

Migraine Disorders

Inactive Indication

Brain InfarctionGlaucoma

Originator Organization

Pfizer Japan, Inc.

Active Organization

Nanjing Changao Pharmaceutical Science & Technology Co. Ltd.

Pfizer Japan, Inc.MSD KK

Inactive Organization

Merck & Co., Inc.

Santen Pharmaceutical Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

JP (12 Mar 1999),

Migraine Disorders

Regulation-

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Structure

Molecular FormulaC27H30F2N2O3

InChIKeyJQSAYKKFZOSZGJ-UHFFFAOYSA-N

CAS Registry101477-55-8

View All Structures (2)

OBJECTIVESCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride.MATERIALS AND METHODSThis is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects.CONCLUSIONWe have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients.REGISTRATIONThe LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

01 Sep 2024·Rapid Communications in Mass Spectrometry

Characterizing Lomerizine metabolites in camel urine: High‐resolution mass spectrometry method development and validation for enhanced doping control

Article

Author: Nagarajan, Erumaipatty Rajagounder ; Hebel, Christiana ; Nalakath, Jahfar ; Waseem, Ibrahim ; Thacholil, Rasik Puzhithinipra ; Kadry, Ahmed ; OK, Praseen ; Selvapalam, Narayanan ; Babu, Ansar

RationaleLomerizine (LMZ) is an antimigraine drug that works as a calcium channel blocker and has selective effects on the central nervous system. It is metabolized into trimetazidine (TMZ), which is a prohibited substance owing to its performance‐enhancing effects in both human and animal sports. Effective doping control measures are imperative to distinguish the source of TMZ in samples to ensure integrity and fairness of the sport, therefore a comprehensive analysis of LMZ metabolites is essential to identify potential biomarkers in camel urine for effective doping control.MethodsCamel urine samples were collected from four healthy animals following a single oral administration of LMZ at a dosage of 1 mg/kg body weight. In vitro studies were conducted using homogenized camel liver samples. Lomerizine and its metabolites were extracted using solid‐phase extraction and analyzed with a Thermo Fisher Orbitrap Exploris liquid chromatography mass spectrometry system. The acquired data was processed with the Compound Discoverer software.ResultsThe study conducted a comprehensive analysis of LMZ metabolites in camels and identified 10 phase I and one phase II metabolites. The primary pathway for the formation of phase I metabolites was de‐alkylation, while phase II metabolite was formed through alkylation of the parent drug. The study provided valuable insights into the unique metabolic pathways of LMZ in camels under specific experimental conditions.ConclusionThe developed method enables the detection and characterization of LMZ and its metabolites in camels. The identified metabolites has the potential to act as marker metabolites for the distinctive detection of LMZ in camel urine to ensure efficient analytical strategies for routine doping control applications.

01 Aug 2024·Drug Testing and Analysis

Doping control analysis of trimetazidine in dried blood spot

Article

Author: Kageyama, Shinji ; Okano, Masato ; Sato, Mitsuhiko ; Miyamoto, Asami ; Ota, Masanori

AbstractDried blood spot (DBS) analysis has been an inherent part of sports drug testing through the technological advancements of the past decade. Trimetazidine, a non‐threshold banned substance, is excreted into urine after a dose of the permitted drug lomerizine. Therefore, a lomerizine‐specific metabolite (M6) is analyzed to confirm the origin of trimetazidine in traditional urine analysis. Application studies were conducted to develop an analytical method for trimetazidine applicable to DBS. These studies comprise (1) the effect of different sampling sites on the detection of trimetazidine, (2) the determination of the appropriate trimetazidine level required for DBS analysis, and (3) differentiating between trimetazidine and lomerizine use. A high‐resolution mass spectrometric method for detecting trimetazidine in DBS was validated. After oral administration of trimetazidine (n = 7), venous and capillary blood (fingertip and upper arm) were spotted on cellulose paper. Trimetazidine could be identified in DBS in all subjects up to 60 h after administration. The limit of detection was 0.05 ng/ml, and the limit of identification was 0.06 ng/ml, suggesting the minimum required performance level of 0.2 ng/ml. In the fingertip capillary blood, biases of 9.7% (vs. upper arm) and 13.0% (vs. vein) were observed in the trimetazidine intensity; however, there were no concerns in the qualitative analysis. After administering lomerizine (n = 10), the intact lomerizine has a strong peak intensity in blood compared to trimetazidine. Contrary to urine analysis, the M6 was less detectable in blood. Laboratories should confirm intact lomerizine whenever trimetazidine is identified in DBS.

100 Deals associated with Lomerizine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D02633	Lomerizine Hydrochloride	N02C	DB14065

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Migraine Disorders	JP	Pfizer Japan, Inc.	12 Mar 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma	Phase 1	JP	-	24 Aug 2003
Brain Infarction	Preclinical	JP	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2014	Not Applicable	Glaucoma, Open-Angle \| Glaucoma	120	Lomerizine 10 mg	tytgxxrqwd(xcmmfplwbd) = oxmeoidxax rdreavzviz (zrphsqiieo )	Positive	01 Apr 2014
				Methylcobalamin 1500 μg	tytgxxrqwd(xcmmfplwbd) = dqpgxiwvpg rdreavzviz (zrphsqiieo )
ARVO2010	Not Applicable	-	9	Nilvadipine	ucevouohzb(bibojxocub) = owyrlxkirx cmsnqcexev (kuajjtwarx )	-	01 Apr 2010
				Lomerizine	ucevouohzb(bibojxocub) = jswuubezko cmsnqcexev (kuajjtwarx )
ARVO2003	Not Applicable	Optic Nerve Injuries	-	Vehicle-treated group	fggkpovvro(fscnlvguhu) = sxlkzvytpx zscfntlvli (boavxsebtv )	Positive	01 May 2003
				Lomerizine 10 mg/kg	fggkpovvro(fscnlvguhu) = bmqqjgocox zscfntlvli (boavxsebtv )