Selective interaction of homophtalazine derivatives with morphine

• Published in: European journal of pharmacology Vol. 331; no. 2; pp. 175 - 183
• Main Authors: Fekete, Márton I.K, Horváth, Katalin, Kedves, Rita, Máté, Ildikó, Székely, József I, Szentkuti, Eszter
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 23-07-1997; Elsevier
• Subjects: Aggression - drug effects; Analgesics, Opioid - pharmacology; Animals; Anti-Anxiety Agents - pharmacology; Anticonvulsants - pharmacology; Anxiolytics; Benzodiazepine; Benzodiazepines - pharmacology; Biological and medical sciences; Catalepsy - chemically induced; Catalepsy - psychology; Dopamine receptor antagonist; Drinking - drug effects; Electroshock; Homophtalazine (2,3-benzodiazepine); Male; Medical sciences; Mice; Mice, Inbred Strains; Morphine - pharmacology; Motor Activity - drug effects; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Neuropharmacology; Opioid; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Reaction Time - drug effects; Seizures - chemically induced; Seizures - prevention & control; Signal transduction; Opioid; Signal transduction; Dopamine receptor antagonist; Anxiolytics; Benzodiazepine; Homophtalazine (2,3-benzodiazepine); Rat; Psychotropic; Rodentia; Central nervous system; Molecular interaction; Morphine; Opiates; Corpus striatum; Tofisopam; Narcotic analgesic; Phthalazine derivatives; Opiate receptor; Vertebrata; Biological fixation; Mammalia; Tranquillizer; Mouse; Girisopam; Animal; Benzodiazepine derivatives; Mechanism of action; Nigrostriatal pathway; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)01056-X

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.