The actions of the novel anti-aggressive drug eltoprazine on central neurones in the anaesthetised rat.
5-Hydroxytryptamine (5-HT) and the novel anti-aggressive drug eltoprazine (1-(2,3-dihydro-1,4-benzodioxin-5-yl) piperazine hydrochloride) were applied by microiontophoresis to spinal motorneurones and also to neurones in the brainstem which gave two distinctly different responses to 5-HT. In vitro microiontophoretic release studies showed that the electrophoretic mobility of eltoprazine and 5-HT were similar and that similar amounts of each drug would be applied by similar iontophoretic currents. Cells in the brainstem have been shown previously to be excited by 5-HT, acting at a 5-HT2 receptor. Eltoprazine only occasionally and weakly mimicked the excitatory effect of 5-HT on these cells. Although a potent antagonism of the 5-HT excitation by eltoprazine was observed, this was a non-selective effect, as responses to glutamate and D,L-homocysteic acid were also reduced. Cells in the lateral brainstem are depressed by 5-HT, acting on a receptor which has previously been shown to be of the 5-HT1-like group. At this receptor, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and 5-carboxamidotryptamine, are potent agonists. Eltoprazine was a more potent depressant agonist than 5-HT on these brainstem neurones. The antagonist metergoline did not antagonise responses to either 5-HT or eltoprazine. It is suggested however that both drugs act at the same receptor to depress these cells because desensitizing the receptor by repeated, frequent applications of 5-HT abolished responses to 5-HT and eltoprazine, without altering responses to GABA.(ABSTRACT TRUNCATED AT 250 WORDS)
Evans
S M
SM
Department of Physiology, University of Wales, College of Cardiff, U.K.
Girdlestone
D
D
Lopez
A
A
Olivier
B
B
Roberts
M H
MH
D000200:Action Potentials / Q000187:drug effects; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D010879:Piperazines; D012701:Serotonin; D018698:Glutamic Acid; C063828:eltoprazine