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SELECTIVE EFFECTS OF LOMERIZINE, A NOVEL DIPHENYLMETHYLPIPERAZINE Ca 2+ CHANNEL BLOCKER, ON CEREBRAL BLOOD FLOW IN RATS AND DOGS
Author(s) -
Hara Hideaki,
Shimazawa Masamitsu,
Sasaoka Masaaki,
Yamada Chikaomi,
Iwakura Yasushi,
Sakai Takanori,
Maeda Yu,
Yamaguchi Takafumi,
Sukamoto Takayuki,
Hashimoto Munehiro
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03154.x
Subject(s) - flunarizine , cerebral blood flow , blood flow , calcium channel blocker , anesthesia , medicine , channel blocker , heart rate , hemodynamics , beagle , blood pressure , pharmacology , calcium
SUMMARY 1. In the present study we examined the effects of a new Ca 2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter). 2. Lomerizine (1.25–10 mg/kg, p.o.) dose‐dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR). 3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., times at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 × 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks. 4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30–120 min after its administration. 5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose‐ dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min. 6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in con‐ditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca 2+ channel blockers.