| Abstrakt: |
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 seizure 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-methylenedioxy-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 1-4h) and (-)2,10,11-trihydroxy-N-ethylnoraporphine (6.25 mg/kg, lasting 2h). 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. Moderate protection against photically-induced myoclonus was seen following 6.25 mg/kg. The order of potency of the compounds in DBA/2 mice and photosensitive baboons was the same. The implications of the results in terms of dopamine receptor structure and function in reflex epilepsy are discussed. [ABSTRACT FROM AUTHOR] |
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