Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene

Su Jane Wang, Kwok Tung Lu, Po Wu Gean

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a longacting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

Original languageEnglish
Pages (from-to)1114-1118
Number of pages5
JournalBritish Journal of Pharmacology
Volume120
Issue number6
DOIs
Publication statusPublished - 1997 Apr 1

Fingerprint

Fluspirilene
Synaptic Transmission
Neurons
Amygdala
Hippocampus
Adenosine A1 Receptor Agonists
Excitatory Postsynaptic Potentials
Membrane Potentials
Anticonvulsants
Antipsychotic Agents
Seizures
Clinical Trials

Keywords

  • Amygdala
  • Epilepsy
  • Fluspirilene
  • Hippocampus
  • Synaptic transmission

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene. / Wang, Su Jane; Lu, Kwok Tung; Gean, Po Wu.

In: British Journal of Pharmacology, Vol. 120, No. 6, 01.04.1997, p. 1114-1118.

Research output: Contribution to journalArticle

@article{01912faa9426460c91dc31924a418257,
title = "Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene",
abstract = "1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a longacting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.",
keywords = "Amygdala, Epilepsy, Fluspirilene, Hippocampus, Synaptic transmission",
author = "Wang, {Su Jane} and Lu, {Kwok Tung} and Gean, {Po Wu}",
year = "1997",
month = "4",
day = "1",
doi = "10.1038/sj.bjp.0701008",
language = "English",
volume = "120",
pages = "1114--1118",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene

AU - Wang, Su Jane

AU - Lu, Kwok Tung

AU - Gean, Po Wu

PY - 1997/4/1

Y1 - 1997/4/1

N2 - 1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a longacting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

AB - 1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a longacting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

KW - Amygdala

KW - Epilepsy

KW - Fluspirilene

KW - Hippocampus

KW - Synaptic transmission

UR - http://www.scopus.com/inward/record.url?scp=0030989748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030989748&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0701008

DO - 10.1038/sj.bjp.0701008

M3 - Article

C2 - 9134224

AN - SCOPUS:0030989748

VL - 120

SP - 1114

EP - 1118

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 6

ER -