Pharmacological profiles of 5-phenylmethylenehydantoin and its methoxy substituted derivatives.
5-Phenylmethylenehydantoin (5-PMH) and 5-(o-methoxyphenyl)methylenehydantoin (5-o-MPMH) were found to have anticonvulsant activities with ED50 values of 48 and 73 mg/kg as compared to 11 mg/kg for phenytoin. The log dose-logit plots yielded nearly parallel straight lines for all three compounds, indicating that they may have the same mechanism of action. The meta- and paramethoxy isomers of 5-o-MPMH, 5-m-MPMH and 5-p-MPMH, did not show any anticonvulsant activity up to 200 mg/kg. In addition, 5-o-MPMH induced neurological deficits as shown by marked effects on rota-rod performance in the dose range of 50-90 mg/kg. Above 100 mg/kg, 5-o-MPMH caused a loss of the righting reflex in mice for up to 2.3 hr at 200 mg/kg. In contrast, 5-PMH, 5-m-MPMH and 5-p-MPMH may have slight sedative effects, but only 5-m-MPMH decreased rota-rod performance significantly at 90 mg/kg. None of the three was hypnotic up to 200 mg/kg in dose. It is therefore inferred that 5-o-MPMH causes general CNS depression via a mechanism distinct from that of its anticonvulsant effects which is shared by phenytoin and 5-PMH. 5-o-MPMH increased jumping latency in the hot plate test in the same dose range as it causes neurological deficit. 5-o-MPMH also appeared to have a similar degree of toxicity in mice as diazepam judging from rough estimates of their LD50/HD85 ratios.
Wong
P T
PT
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Kent Ridge.
Tan
S F
SF
D000700:Analgesics; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004597:Electroshock; D006827:Hydantoins / Q000494:pharmacology* / Q000633:toxicity; D006993:Hypnotics and Sedatives; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D000700:Analgesics; D000927:Anticonvulsants; D006827:Hydantoins; D006993:Hypnotics and Sedatives; C060379:5-(2-methoxyphenyl)methylenehydantoin; C060378:5-phenylmethylenehydantoin