Antagonism of maximal metrazol seizures in rats and its relevance to an experimental classification of antiepileptic drugs.
The antagonism of various components of maximal Metrazol-seizures (MMS) (i.e. tonic hindpaw extension, tonic backward extension of the forepaws, generalized clonic seizures and tremors), ataxia and loss of righting reflex-activity have been studied in a standardized procedure comparing 41 antiepileptics and related compounds. Appropriate analyses (Cluster Analysis and Principal Component Analysis) resulted in the distinction of seven clusters which could be considered along two continua. A first continuum is characterized by a progressive strengthening of loss of righting reflex-inducing properties, a decreasing dissociation of ataxia and loss of righting reflex and the disappearance of a selective anticonvulsant effect. The second continuum is characterized by an increasing relative potency of ataxia-inducing properties, an increasing dissociation of ataxia and loss of righting reflex and a decreasing antagonism of tremors. Three main types of anticonvulsants could be defined: drugs with a complete anti-MMS effect antagonizing both clonic and tonic seizures; drugs selectively abolishing tonic seizures, i.e., tonic extension of hind- and forepaws; and drugs exclusively blocking tonic hind-paw extension. The neurological and clinical significance of these different types of anticonvulsant activity has been discussed. Finally, the described modification of the maximal Metrazol-seizures test is proposed for routine screening purposes.
D000818:Animals; D000927:Anticonvulsants / Q000145:classification* / Q000494:pharmacology; D001259:Ataxia / Q000139:chemically induced; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D014202:Tremor / Q000139:chemically induced
D000927:Anticonvulsants; D010433:Pentylenetetrazole