1.[Metabolism of lomerizine hydrochloride (KB-2796) in rats].
Awata N1, Sakai T, Satomi O, Kawashima T. Yakugaku Zasshi. 1995 Feb;115(2):120-9.
The metabolism of lomerizine was investigated after the oral administration of [methine-14C] or [benzyl-14C]lomerizine hydrochloride in rats. 1. Urinary, fecal and biliary excretions of the unchanged drug were less than 1% of dose, showing that lomerizine was eliminated by the extensive biotransformation after the oral administration. 2. The main metabolites were 1-(2,3,4-trimethoxybenzyl)piperazine (M7) and 2,3-dimethoxy-4-hydroxybenzylpiperazine in the urine, and 1-[bis(4-fuluorophenyl)methyl]-4-(2,3-dimethoxy-4-hydroxybenzyl)pi perazine in the feces and bile. 3. The radioactive substances in the plasma, liver and brain mainly existed as unconjugated forms, of which the intact drug showed the highest concentration. 4. The main metabolites in the plasma, and in the liver and brain were 1-[bis(4-fuluorophenyl)methyl]-4-(3,4-dimethoxy-2-hydroxybenzyl)pi perazine and bis(4-fluorophenyl)methylpiperazine (M6), respectively. 5. The plasma level of M7 and the biliary excretion of bis(4-fluorophenyl)-methanol in male rats were higher than those in female rats, suggesting the sex difference in the N-dealkylation at the 4-position of piperazine ring of the drug.
2.[A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which lomerizine hydrochloride was suggested to prevent recurrent stroke].
Shimizu H1, Nagami S, Takahashi N. Rinsho Shinkeigaku. 2014;54(1):22-6.
A 60-year-old man visited our hospital because of left hemiparesis in September 2006. Magnetic resonance imaging (MRI) revealed a high-intensity lesions in the right corona radiata on diffusion-weighted images and a high-intensity lesions in the basal ganglia and deep white matter on T2-weighted images. He recovered with no sequelae. Antithrombotic agents such as aspirin were given to prevent stroke, but stroke recurred three times over the course of 3 years. In February 2009, neurological examination revealed right hemiparalysis and dysarthria. Dysphagia and cognitive decline had been progressing gradually. We suspected cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) on the basis of the clinical and family history. An Arg75Pro mutation in the Notch3 gene was found, but did not involve a cysteine residue. Antithrombotic agents were ineffective. We tried lomerizine hydrochloride, which was reported to prevent stroke in a patient with CADASIL.
3.Preventive effect of cyproheptadine hydrochloride in refractory patients with frequent migraine.
Okuma H1, Iijima K, Yasuda T, Tokuoka K, Kitagawa Y. Springerplus. 2013 Oct 29;2:573. doi: 10.1186/2193-1801-2-573. eCollection 2013.
Cyproheptadine hydrochloride (CH) is rarely used to treat adult patients with migraine in Japan because it causes sleepiness. In this study, we investigated the preventive effect of CH in 12 patients who had failed to respond to conventional preventive treatments among 103 migraine patients treated at our hospital. These 12 subjects had all received unsuccessful migraine prophylaxis with lomerizine, valproic acid and topiramate, or had discontinued these treatments due to adverse reactions. Initially, the subjects were given 4 mg CH before sleeping. In those who experienced no clinically significant sleepiness following the treatment, the drug was orally administered at 4 mg after breakfast as well (8 mg per day in total). Drug efficacy was evaluated by examining the frequency of migraine at one month and three months after the start of treatment. The frequency of migraine was dramatically reduced in all patients within 7 to 10 days after starting treatment.