EGYT-2509 a novel neuroleptic agent without extrapyramidal and endocrine side effects.
The dibenzodioxazocine derivative EGYT-2509 was effective in neuropsychopharmacological tests characteristic for neuroleptics and antiparkinsonian drugs. It interacted with dopaminergic compounds similarly to chlorpromazine and haloperidol, but in certain tests it showed different activity. Similarly to chlorpromazine and haloperidol it inhibited the lethal effect of amphetamine in grouped mice. The apomorphine-induced stereotypy was potentiated by lower, and antagonized by higher doses of EGYT-2509. The compound did not show cataleptogenic activity and even antagonized the catalepsy evoked by bulbocapnine. The in vitro potency of EGYT-2509 to block dopamine-mediated inhibition of prolactin release was weaker by three orders of magnitude than that of haloperidol. In preliminary human studies it did not affect the plasma prolactin level. It is concluded that EGYT-2509 is a new potential antipsychotic agent with minimal risk of extrapyramidal and endocrine side effects.
Gacsályi
I
I
EGIS Pharmaceuticals, Budapest, Hungary.
Petöcz
L
L
Fekete
M I
MI
Bükkfálvi
B
B
Görgenyi
F
F
Arató
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001060:Aporphines / Q000494:pharmacology; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000503:physiopathology; D002375:Catalepsy / Q000139:chemically induced; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D003989:Dibenzoxazepines / Q000009:adverse effects / Q000494:pharmacology*; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D014150:Antipsychotic Agents; D001060:Aporphines; D003989:Dibenzoxazepines; C049176:EGYT 2509; D011388:Prolactin; D001058:Apomorphine; D003913:Dextroamphetamine