The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones

Kevin Lee, F McKenna, I C Rowe, M L Ashford

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca(2+)-activated K+ (BKCa) 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 BKCa 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 BKCa channel activity (100 nM-1 mM) in either inside-out or outside-out patches, while 10 microM pimozide produced 73% of the inhibition produced by 10 microM chlorpromazine. 4. BKCa 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 BKCa 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 BKCa 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.
    Original languageEnglish
    Pages (from-to)1810-6
    Number of pages7
    JournalBritish Journal of Pharmacology
    Volume121
    Issue number8
    DOIs
    Publication statusPublished - Aug 1997

    Fingerprint

    Antipsychotic Agents
    Neurons
    Chlorpromazine
    Motor Cortex
    Pimozide
    Tacrine
    Sulpiride
    Amitriptyline
    Clozapine
    Tricyclic Antidepressive Agents
    Cholinesterase Inhibitors
    Carbamazepine
    Haloperidol
    Drug Therapy

    Keywords

    • Rats
    • Cerebral Cortex
    • Animals
    • Rats, Sprague-Dawley
    • Calcium
    • Antipsychotic Agents
    • Potassium Channels
    • Male
    • Antidepressive Agents, Tricyclic

    Cite this

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    abstract = "1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca(2+)-activated K+ (BKCa) 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 BKCa 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 BKCa channel activity (100 nM-1 mM) in either inside-out or outside-out patches, while 10 microM pimozide produced 73{\%} of the inhibition produced by 10 microM chlorpromazine. 4. BKCa 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 BKCa 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 BKCa 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.",
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    author = "Kevin Lee and F McKenna and Rowe, {I C} and Ashford, {M L}",
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    The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones. / Lee, Kevin; McKenna, F; Rowe, I C; Ashford, M L.

    In: British Journal of Pharmacology, Vol. 121, No. 8, 08.1997, p. 1810-6.

    Research output: Contribution to journalArticle

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    T1 - The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones

    AU - Lee, Kevin

    AU - McKenna, F

    AU - Rowe, I C

    AU - Ashford, M L

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    N2 - 1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca(2+)-activated K+ (BKCa) 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 BKCa 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 BKCa channel activity (100 nM-1 mM) in either inside-out or outside-out patches, while 10 microM pimozide produced 73% of the inhibition produced by 10 microM chlorpromazine. 4. BKCa 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 BKCa 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 BKCa 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.

    AB - 1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca(2+)-activated K+ (BKCa) 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 BKCa 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 BKCa channel activity (100 nM-1 mM) in either inside-out or outside-out patches, while 10 microM pimozide produced 73% of the inhibition produced by 10 microM chlorpromazine. 4. BKCa 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 BKCa 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 BKCa 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.

    KW - Rats

    KW - Cerebral Cortex

    KW - Animals

    KW - Rats, Sprague-Dawley

    KW - Calcium

    KW - Antipsychotic Agents

    KW - Potassium Channels

    KW - Male

    KW - Antidepressive Agents, Tricyclic

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