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The effects of neuroleptic and tricyclic compounds on BK Ca channel activity in rat isolated cortical neurones
Author(s) -
Lee K,
McKenna F,
Rowe I. C. M.,
Ashford M. L. J.
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.0701333
Subject(s) - tricyclic , haloperidol , chlorpromazine , chemistry , pharmacology , amitriptyline , sulpiride , nortriptyline , clozapine , medicine , biochemistry , dopamine , antagonist , schizophrenia (object oriented programming) , receptor , psychiatry
1 The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca 2+ ‐activated K + (BK Ca ) channel present in neurones isolated from the rat motor cortex. 2 Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside‐out patches produced a concentration‐dependent reduction in BK Ca channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside‐out patches. 3 In contrast, the atypical neuroleptic compounds clozapine and sulpiride did not affect BK Ca channel activity (100 n M –1 m M ) in either inside‐out or outside‐out patches, while 10 μ M pimozide produced 73% of the inhibition produced by 10 μ M chlorpromazine. 4 BK Ca channel activity was also unaffected by application of structurally related tricyclic compounds including the anti‐cholinesterase tacrine and the anti‐epileptic carbamazepine. The tricyclic antidepressant drug amitriptyline was found to inhibit BK Ca channel activity but was much less effective than the classical neuroleptic compounds. 5 It is concluded that compounds belonging to the classical neuroleptic group of drugs inhibit BK Ca channel activity in the rat motor cortex in a structurally‐specific manner. This observation may be of clinical significance as it may contribute to some of the side effects associated with classical neuroleptic drug therapy.British Journal of Pharmacology (1997) 121 , 1810–1816; doi: 10.1038/sj.bjp.0701333