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Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene
Author(s) -
Wang SuJane,
Lu KwokTung,
Gean PoWu
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701008
Subject(s) - neurotransmission , excitatory postsynaptic potential , postsynaptic potential , neuroscience , chemistry , neural facilitation , hippocampus , agonist , inhibitory postsynaptic potential , pharmacology , receptor , biology , biochemistry
Recent studies have shown that fluspirilene, a dopamine D 2 receptor antagonist which is a long‐acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca 2+ 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. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f‐e.p.s.p) in a concentration‐dependent manner in the area CAl 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. Fluspirilene increased the ratio of paired‐pulse facilitation suggesting a presynaptic mode of action. 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 A 1 receptor agonist, N 6 ‐cyclopentyladenosine (CPA). It is concluded that fluspirilene‐induced synaptic inhibition is probably due to a reduction in presynaptic Ca 2+ 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.British Journal of Pharmacology (1997) 120 , 1114–1118; doi: 10.1038/sj.bjp.0701008