Anticonvulsant effects of U-54494A and U-50488H in genetically epilepsy-prone rats and DBA/2 mice: a possible involvement of glycine/NMDA receptor complex.
1. The effects of U-54494A and U-50488H on convulsions produced by sound have been studied in genetically epilepsy-prone DBA/2 mice and genetically epilepsy-prone rats. 2. Both compounds showed a dose-dependent anticonvulsant activity. U-54494A was less potent as an anticonvulsant than U-50488H in genetically epilepsy-prone rats and elicited a similar potency to that of U-50488H in DBA/2 mice when administered intracerebroventricularly or intraperitoneally. 3. Similar sedative and hypothermic effects were observed after the highest dose of U-54494A and U-50488H in DBA/2 mice. U-50488H seems to exhibit a greater sedative effect and to affect the rotarod test in rats much more than U-54494A. U-54494A elicited a better therapeutic index than U-50488H. 4. The anticonvulsant properties of both compounds are antagonized by high doses of naloxone and nor-binaltorphimine, a selective kappa-opioid antagonist. 5. The effects of U-50488H and U-54494A in DBA/2 mice were also antagonized by the glycine/NMDA receptor antagonist D-serine. 6. The present results suggest a possible interaction between kappa-opioid and the glycine/NMDA receptors during epileptic phenomena.
Department of Experimental and Clinical Medicine, University of Reggio Calabria, Italy.
G
G
De Sarro
G R
GR
Trimarchi
S
S
Sinopoli
Y
Y
Masuda
A
A
De Sarro
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004827:Epilepsy / Q000517:prevention & control*; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D012694:Serine / Q000494:pharmacology
D000927:Anticonvulsants; D011759:Pyrrolidines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D012694:Serine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C054216:U 54494A