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Behavioural hyperactivity in rats treated with selective monoamine oxidase inhibitors and LM 5008, a selective 5‐hydroxytryptamine uptake blocker
Author(s) -
Ashkenazi R.,
Finberg J.P.M.,
Youdim M.B.H.
Publication year - 1983
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 - 10.1111/j.1476-5381.1983.tb10015.x
Subject(s) - tranylcypromine , monoamine oxidase , pharmacology , monoamine oxidase inhibitor , chemistry , imipramine , medicine , biochemistry , enzyme , alternative medicine , pathology
1 The administration of 4‐[2‐(3‐indolyl)ethyl]piperidine (LM 5008), a selective 5‐hydroxytryptamine (5‐HT) uptake blocker to rats pretreated with tranylcypromine (Tcp) resulted in a behavioural syndrome of locomotor hyperactivity which is indistinguishable from that following combined treatment with Tcp and l ‐tryptophan. 2 A similar behavioural response was elicited by the administration of LM 5008 to rats pretreated with 5‐hydroxytryptophan. 3 The response to LM 5008 after monoamine oxidase (MAO) inhibition was abolished by pretreatment with p ‐chlorophenylalanine, indicating the involvement of 5‐HT in producing the hyperactivity syndrome. 4 The administration of imipramine and chlorimipramine in combination with Tcp also resulted in hyperactivity, but these drugs were much less potent than LM 5008 in producing the syndrome. 5 In contrast to l ‐tryptophan, which can produce hyperactivity only after the inhibition of both type A and type B MAO, LM 5008 can elicit the syndrome after selective inhibition of MAO type A only but not after inhibition of MAO type B. 6 The behavioural results indicate that when MAO type A is inhibited, LM 5008 treatment elicits hyperactivity by preventing the availability of 5‐HT to be metabolized by MAO‐B component.