Clinical effect of WEB 1881 (nebracetam fumarate) on patients with dementia of the Alzheimer type and study of its clinical pharmacology.
We administrated WEB 1881, 800 mg/day (400 mg twice a day), nine patients with dementia of the Alzheimer type for 8 weeks, and undertook an open study to investigate the clinical effects of the distribution into the cerebrospinal fluid (CSF) as well as the influence on the neurotransmitter-related substances in the CSF. These were outpatients living at home with caregivers. Significant clinical improvement was shown by means of the Gottfries, Bråne, and Steen Scale and by Hasegawa's dementia scale. Unchanged WEB 1881 was identified in the CSF. The mean concentration of which was 198.7 ng/ml, this corresponded to 19.0% of the plasma concentration. Of several neurotransmitter-related substances measured in the CSF, a marked rise of AChE activity was observed. Adverse effects consisted of a slight skin eruption in one case and alterations in a clinical laboratory test in another case. These were, however, not significant from a clinical viewpoint. It is suggested that the mechanisms of action of WEB 1881 are based on its transit into the CSF as well as the activation of intracerebral acetylcholinergic systems.
Urakami
K
K
Division of Neurology, Faculty of Medicine, Tottori University, Yonago City, Japan.
Shimomura
T
T
Ohshima
T
T
Okada
A
A
Adachi
Y
Y
Takahashi
K
K
Asakura
M
M
Matsumura
R
R
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid; D011619:Psychotropic Drugs / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*
D018377:Neurotransmitter Agents; D011619:Psychotropic Drugs; D011760:Pyrrolidinones; C056640:nebracetam