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
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
Molecular Formula | C27H30F2N2O3 |
Molecular Weight | 468.5355 |
Charge | 0 |
Count |
MOL RATIO
1 MOL RATIO (average) |
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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
PubMed
Patents
Sample Use Guides
Oral 5 mg lomerizine or placebo was administered to volunteers (n=8) in a crossover study
Route of Administration:
Oral
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