Selective interaction of homophtalazine derivatives with morphine.
Homophtalazines show specific binding sites in the nigrostriatal system and to find their target of action the interactions between these derivatives, nerisopam and girisopam, and chlorpromazine, chlordiazepoxide and morphine were assessed. The compounds did not influence the chlorpromazine induced decrease in motility and catalepsy, nor did they alter the antiaggressive and anticonvulsive action of chlordiazepoxide. However, nerisopam and girisopam augmented the agonist potency of morphine to induce catalepsy or analgesia; they also altered the opioid antagonist potency of naloxone. The naloxone-induced decrease in sucrose consumption in drinking water was augmented by nerisopam and girisopam. It is suggested that a possible target of action of homophtalazines is the opioid signal transduction.
Fekete
M I
MI
EGIS Pharmaceuticals Ltd., Budapest, Hungary. fekete@koki.hu
Horváth
K
K
Kedves
R
R
Máté
I
I
Székely
J I
JI
Szentkuti
E
E
D000374:Aggression / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D004326:Drinking / Q000187:drug effects; D004597:Electroshock; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D009292:Narcotic Antagonists; D001569:Benzodiazepines; C061627:Nerisopam; C045445:girisopam; D009270:Naloxone; D009020:Morphine