Pharmacological profile of the novel putative anxiolytic agent 1-amino-5-bromouracil.
The newly synthesized compound, 1-amino-5-bromouracil (ABU, CAS 127984-93-4), showed unique anxiolytic activity in rats and mice. Its minimum effective dose was 10 mg/kg p.o. in the Geller type conflict test in rats, and it showed anxiolytic activity at a dose of 20 mg/kg i.p. in the Vogel type conflict test in mice. ABU also induced loss of the righting reflex in mice. The ED50, a dose level that induces loss of the righting reflex in 50% of mice, was 86.4 mg/kg p.o. On the other hand, ABU showed only weak activities both potentiating the drug-induced anesthesia and myorelaxing in comparison with diazepam. Furthermore ABU did not show an affinity for benzodiazepine receptor. Thus, the pharmacological profile of ABU is concluded to be different from that of diazepam.
Imaizumi
M
M
Biology Laboratory, Research & Development Division, Yamasa Corp., Chiba, Japan.
Miyazaki
S
S
Watanabe
Y
Y
Machida
H
H
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001976:Bromouracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D003220:Conflict, Psychological; D003975:Diazepam / Q000493:pharmacokinetics / Q000494:pharmacology; D004357:Drug Synergism; D005445:Flunitrazepam / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects
D000777:Anesthetics; D014151:Anti-Anxiety Agents; D009125:Muscle Relaxants, Central; D011963:Receptors, GABA-A; D001976:Bromouracil; D005445:Flunitrazepam; C087307:1-amino-5-bromouracil; D003975:Diazepam