Effects of sigma ligands on mouse cerebellar cyclic guanosine monophosphate (cGMP) levels in vivo: further evidence for a functional modulation of N-methyl-D-aspartate (NMDA) receptor complex-mediated events by sigma ligands.
In the present investigation, the effects of sigma ligands [WY-47384 [8-fluoro-2,3,4,5-tetrahydro-2[3-(3-pyridinyl)propyl)1H- pyrido(4,3b)indole], (+)-pentazocine, (+)-SFK 10,047 (N-allylnormetazocine), mafoprazine, opipramol, dextromethorphan, dextrorphan, (+)-3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine], (-)-butaclamol, DTG [1,3-di(2-tolyl)guanidine], rimcazole, ifenprodil and BMY-14802 [alpha-(fluorophenyl)-4-(5-fluoropyrimidinyl)-1-piperazine butanol]] on harmaline-, pentylenetetrazol (PTZ)-, methamphetamine (MA)- and D-serine-induced increases in mouse cerebellar levels of cGMP were determined. Ifenprodil, BMY-14802, dextromethorphan, dextrorphan, (+)-SKF 10,047, opipramol and mafoprazine reversed harmaline-, PTZ-, MA- and D-serine-induced increases in levels of cGMP. Rimcazole reversed only the harmaline-induced response. WY-47384 reversed harmaline-, MA-, D-serine-, but not PTZ- or quisqualate-induced increases in levels of cGMP. (+)-Pentazocine attenuated harmaline- and D-serine-, but not PTZ- and MA-induced cGMP responses. Haloperidol did not affect harmaline- and D-serine-induced cGMP responses. (+)-3-PPP and (-)-butaclamol did not affect any of the responses studied. Furthermore, (+)-3-PPP-induced increases in levels of cGMP were reversed by the competitive N-methyl-D-aspartate (NMDA) antagonist, CPP]3-(2-carboxypiperazin-4-yl)propyl- 1-phosphonic acid, the non-competitive NMDA antagonist, (+)-MK-801 (dizocilipine maleate), the NMDA-associated glycine receptor antagonist, HA-966 (3-amino-1-hydroxypyrrolidin-2-one), the partial glycine agonist, DCS (D-cycloserine) as well as by the sigma ligands, ifenprodil, WY-47384, (+)-pentazocine, (+)-SKF 10,047, dextromethorphan and dextrorphan but not by rimcazole.(ABSTRACT TRUNCATED AT 250 WORDS)
Searle Research and Development, G.D. Searle-Monsanto Co., St. Louis, MO 63198.
T S
TS
Rao
S J
SJ
Mick
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JA
Cler
M R
MR
Emmett
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Dilworth
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Contreras
N M
NM
Gray
P L
PL
Wood
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Iyengar
D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D015259:Dopamine Agents / Q000037:antagonists & inhibitors; D006246:Harmaline / Q000037:antagonists & inhibitors; D008024:Ligands; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000037:antagonists & inhibitors; D016318:Quisqualic Acid / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D012694:Serine / Q000037:antagonists & inhibitors
D015259:Dopamine Agents; D008024:Ligands; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017480:Receptors, sigma; D008694:Methamphetamine; D012694:Serine; D016318:Quisqualic Acid; C026539:preclamol; D006246:Harmaline; D006152:Cyclic GMP; D010433:Pentylenetetrazole