D1 agonists suppress zero Mg(2+)-induced epileptiform activity in the rat cingulate cortex slice.
This study determined whether dopamine can influence epileptiform activity in vitro through an action at D1 receptors. Dopamine (50-1000 microM) and the selective D1 agonists SKF 38393, SKF 75670, SKF 80723 and SKF 82526 (10-250 microM) suppressed the paroxysmal discharges produced in rat cingulate cortex slices by the omission of Mg2+ from the bathing medium. These antiepileptic effects were mimicked by forskolin (10-100 microM), blocked by the D1 antagonist SCH 39166 (0.5 microM), facilitated by IBMX (500 microM) and unaffected by propranolol (2 microM), suggesting the participation of cyclic AMP in the D1 response. Possible mechanisms, including direct postsynaptic inhibition, modulatory enhancement of GABA activity and presynaptic inhibition of glutamate release are considered.
Alam
A M
AM
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
M S
MS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D018818:Fenoldopam; D066298:In Vitro Techniques; D008274:Magnesium / Q000633:toxicity*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; C058081:ecopipam; D005576:Colforsin; C052506:SK&F 75670; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011433:Propranolol; D008274:Magnesium; D018818:Fenoldopam; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine