Interactions of apomorphine and a novel neuroleptic dibenzodioxazocine derivative, as evidenced by changes of somato-autonomic reflexes and spontaneous sympathetic activity in cats.
The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg-1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0.2 mg kg-1 i.v.) at low frequencies of stimuli (2-8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1.5 mg kg-1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1.5 mg kg-1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18.5 mg kg-1): after EGYT-2509, higher doses of apomorphine (0.7 vs 0.2 mg kg-1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8.5 vs 18.5 mg kg-1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg-1 i.p., respectively), apomorphine (0.2 mg kg-1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Dóda
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Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002746:Chlorpromazine / Q000494:pharmacology; D003989:Dibenzoxazepines / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D014150:Antipsychotic Agents; D003989:Dibenzoxazepines; C049176:EGYT 2509; D006220:Haloperidol; D001058:Apomorphine; D002746:Chlorpromazine