Inhibitory effects of etoperidone on the spontaneous activity of brainstem neurones and their excitatory responses to some putative transmitters.
In this microiontophoretic study delta 2,1,2,4-triazolin-5-one [1,3-(4-m-chlorophenyl-1-piperazinyl) propyl]-3,4-diethyl hydrochloride (etoperidone, ET, Staff) was applied on rat brainstem (medullary-pontine) reticular neurones to verify its effects on the spontaneous firing and neuronal responses to administrations of 5-hydroxytryptamine (5HT), noradrenaline (norepinephrine, NA), acetylcholine (ACh) and gamma-aminobutyric acid (GABA). ET was able to depress the spontaneous firing by a dose-dependent (for a current intensity range of 40-70 nA) local anaesthetic-like mechanism. At 75 nA a reduction in the amplitude of the action potentials occurred, partially due to a non-specific effect of ET. Repeated administrations of ET caused a progressive neuronal desensitization to the inhibition (tachyphylaxis). All the excitatory neuronal responses to ACh, 5HT and NA (interpreted respectively as nicotinic cholinergic, alpha-noradrenergic, 5HT3-serotonergic) were blocked by ET, while the inhibitory responses to 5HT, NA and GABA were not affected. The analysis of the results leads to postulate for ET a postsynaptic mechanism of action.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects*; D005260:Female; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014196:Trazodone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; C013528:etoperidone; D014196:Trazodone