Comparative assessment of dopamine agonist aporphines as anticonvulsants in two models of reflex epilepsy.
The anticonvulsant action of various aporphine derivatives that act on dopamine receptors has been investigated in two genetically determined animal models--DBA/2 mice with sound-induced seizures and baboons Papio papio with photically-induced seizures. Protection against the clonic and tonic phases of the seizures response in DBA/2 mice was seen for 15-60 min after (-)2,10,11-trihydroxy-N-n-propylnoraporphine (1.25 mg/kg) and (-)10,11-methyl-enedioxy-N-n-propylnoraporphine (0.625-1.25 mg/kg) and for 30-60 min after (-)2,10,11-trihydroxyaporphine (31.25 mg/kg). Short-lasting protection (up to 30 min) was seen following (-)2,10,11-trihydroxy-N-ethyl-noraporphine (1.25-6.25 mg/kg). Changes in audiogenic seizure susceptibility were accompanied by piloerection, ptosis and loss of spontaneous locomotor and exploratory behaviour. No protection was seen after (-)norapomorphine (0.05-18.75 mg/kg). All the compounds (including norapomorphine) significantly lowered rectal temperature, although the time course of this effect was often longer than that of protection against audiogenic seizures. In baboons, marked reductions in photomyoclonic responses were seen following (-)10,11-methylenedioxy-N-n-propylnoraporphine (0.25 mg/kg, lasting up to 2h); (-)2,10,11-trihydroxy-N-n-propylnoraporphine (0.5-2.5 mg/kg, lasting up to 7 h); (-)2,10,11-trihydroxyaporphine (5 mg/kg, duration of action 1-4 h) and (-)2,10,11-trihydroxy-N-ethylnoraporphine (6.25 mg/kg, lasting 2 h). Little change in responsiveness followed administration of (-)norapomorphine 1.25 or 6.25 mg/kg. Changes in photosensitivity were accompanied by yawning and pupil dilatation. (-)10,11-Methylenedioxy-N-n-propylnoraporphine (0.5-6.25 mg/kg) was also administered orally in baboons.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000927:Anticonvulsants; D001060:Aporphines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010215:Papio; D011954:Receptors, Dopamine / Q000187:drug effects*; D013997:Time Factors
D000927:Anticonvulsants; D001060:Aporphines; D011954:Receptors, Dopamine