LOMERIZINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H30F2N2O3
Molecular Weight	468.5355
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(CN2CCN(CC2)C(C3=CC=C(F)C=C3)C4=CC=C(F)C=C4)C(OC)=C1OC

InChI

InChIKey=JQSAYKKFZOSZGJ-UHFFFAOYSA-N

InChI=1S/C27H30F2N2O3/c1-32-24-13-8-21(26(33-2)27(24)34-3)18-30-14-16-31(17-15-30)25(19-4-9-22(28)10-5-19)20-6-11-23(29)12-7-20/h4-13,25H,14-18H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C27H30F2N2O3
Molecular Weight	468.5355
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/24074550
Curator's Comment: description was created based on several sources, including: http://www.alomone.com/p/lomerizine_dihydrochloride_/l-125/7 http://www.ncbi.nlm.nih.gov/pubmed/15492768

Lomerizine (INN) (also known as KB-2796) is a diphenylpiperazine class L-type and T-type calcium channel blocker with relatively selective CNS effects. Voltage dependent L-type Ca2+ channels play an important role Ca2+ influx. L-type calcium currents typically require a strong depolarization for activation and are long-lasting. The common pharmacological profile of L-type channels is determined by the α1 subunit, which forms the Ca2+ selective. Lomerizine was developed as a potential agent for the selective improvement of the ocular or cerebrovascular circulation with minimal adverse cardiovascular effects, and it is used as an anti- migraine drug. Lomerizine selectively relaxes smooth muscle cells by inhibiting L-type Ca2+ influx, thereby reducing tone and increasing blood flow in cerebral vessels. Lomerizine also shows neuroprotective effects against secondary degeneration resulting from injury in retinal ganglion cells. While some calcium-channel blockers, such as flunarizine, act on the dopaminergic system, lomerizine is ineffective in vivo at inhibiting the release of dopamine. However, it has been observed to weakly inhibit the binding of [3H]spiperone to D2 dopamine receptors in vitro. While researchers are unsure of the reason for this difference, one hypothesis is that the doses administered cannot reach a high enough concentration in the brain to affect D2 receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel 95 Target ID: CHEMBL2095229 Sources: http://www.alomone.com/p/lomerizine_dihydrochloride_/l-125/7	Blocker 555
Voltage-gated T-type calcium channel 19 Target ID: CHEMBL2362995 Sources: http://www.ncbi.nlm.nih.gov/pubmed/21112351	Blocker 555

Conditions

Condition	Modality	Targets	Highest Phase	Product
Glaucoma 57 Sources: http://www.ncbi.nlm.nih.gov/pubmed/15492768	Primary		Phase II 1147	Unknown Approved Use Unknown
Migraine 107 Sources: http://www.ncbi.nlm.nih.gov/pubmed/24291939	Primary		Approved 8583	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
9.06 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24412691/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.3 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.7 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
15.7 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
31.3 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
74.22 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24412691/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
40.7 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
45.5 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
83.9 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
183.1 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
5.48 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24412691/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.4 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.6 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=29	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	LOMERIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
22% EXPERIMENT https://www.info.pmda.go.jp/go/interview/5/672212_2190023F1037_5_1F.pdf#page=30			LOMERIZINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18340570/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18340570/	Disc. AE: Fatigue... AEs leading to discontinuation/dose reduction: Fatigue (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/18340570/

AEs

AE	Significance	Dose	Population
Fatigue	3% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18340570/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18340570/

PubMed

Title	Date	PubMed
Interaction of CJZ3, a lomerizine derivative, with ATPase activity of human P-glycoprotein in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.	2010-07	20662321
Lomerizine, a Ca2+ channel blocker, protects against neuronal degeneration within the visual center of the brain after retinal damage in mice.	2010-04	19788586
Limited restoration of visual function after partial optic nerve injury; a time course study using the calcium channel blocker lomerizine.	2010-03-16	19913075
Early events of secondary degeneration after partial optic nerve transection: an immunohistochemical study.	2010-02	19852581
Scaffold-based design and synthesis of potent N-type calcium channel blockers.	2009-11-15	19815411
Secondary retinal ganglion cell death and the neuroprotective effects of the calcium channel blocker lomerizine.	2009-11	19474405
[New developments in glaucoma medical treatment].	2009-10	19902393
Inhibitory effect of lomerizine, a prophylactic drug for migraines, on serotonin-induced contraction of the basilar artery.	2009-10	19783864
Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine.	2009-06-11	19512965
Secondary degeneration of the optic nerve following partial transection: the benefits of lomerizine.	2009-03	19118550
[Migraine improved by amlodipine medication in a case with hypertension].	2008-09	19057109
Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa.	2008-04-16	18412981
Migraine-associated vertigo: clinical characteristics of Japanese patients and effect of lomerizine, a calcium channel antagonist.	2007-12	18340570
[Cluster like headache in a patient with the Maffucci's syndrome].	2006-06	16856522
CJZ3, a lomerizine derivative, modulates P-glycoprotein function in rat brain microvessel endothelial cells.	2006-04	16539840
A new calcium channel antagonist, lomerizine, alleviates secondary retinal ganglion cell death after optic nerve injury in the rat.	2006-03	16531285
Neuroprotective effect of calcium channel blocker against retinal ganglion cell damage under hypoxia.	2006-02-03	16413513
[Prophylactic treatment of migraine].	2005-10	16218395
[Reversal of multidrug resistance by lomerizine in K562/ADM cells].	2004-05	15338873
Clinical potential of lomerizine, a Ca2+ channel blocker as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage.	2004	15492768
Effects of lomerizine, a calcium channel antagonist, on retinal and optic nerve head circulation in rabbits and humans.	2003-11	14578410
Validation of scanning laser Doppler flowmetry for retinal blood flow measurements in animal models.	2002-05	12434302
Increase in doxorubicin cytotoxicity by inhibition of P-glycoprotein activity with lomerizine.	2001-05	11379779
Effects of lomerizine, a novel Ca2+ channel blocker, on the normal and endothelin-1-disturbed circulation in the optic nerve head of rabbits.	2001-04	11324981

Patents

Sample Use Guides

In Vivo Use Guide

Oral 5 mg lomerizine or placebo was administered to volunteers (n=8) in a crossover study

Route of Administration: Oral

In Vitro Use Guide

In rat cortical membrane, KB-2796 (LOMERIZINE) inhibited specific [3H]spiperone binding to 5-HT2 receptors in a competitive manner (Ki = 0.57 uM), but exhibited negligible affinity for radioligand binding to other 5-HT receptor subtypes such as 5-HT1, 5-HT1A, 5-HT1B, 5-HT1C and 5-HT3 at a concentration of 10 or 100 uM. KB-2796 also inhibited the 5-HT-induced increase of [Ca2+]i in washed rabbit platelets with the IC50 value of 25.7 uM

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:46:28 GMT 2025` Edited by `admin` on `Wed Apr 02 09:46:28 GMT 2025`
Record UNII	DEE37CY4VO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LOMERIZINE [MI]

Preferred Name

English

LOMERIZINE

Official Name

English

Lomerizine [WHO-DD]

Common Name

English

lomerizine [INN]

Common Name

English

1-(BIS(P-FLUOROPHENYL)METHYL)-4-(2,3,4-TRIMETHOXYBENZYL)PIPERAZINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333