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Effects of phenothiazines and dibenzazepines on axonal transport and microtubule assembly in vitro

EKSTRÖM, Per LU ; KANJE, Martin LU and EDSTRÖM, Anders LU (1982) In Acta Physiologica Scandinavica 116(2). p.121-125
Abstract

Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (3H) leucine‐labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The... (More)

Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (3H) leucine‐labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The polymerization of purified brain tubulin was inhibited by the phenothiazines but unaffected by the dibenzazepines at concentrations which inhibited AXT. Phenothiazines and dibenzazepines are chemically related and known to have a high affinity for calmodulin. The possibility that these drugs interefere with calmodulin regulated processes of importance for AXT will be discussed.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
axonal transport, calmodulin, dibenzazepines, frog sciatic nerve, microtubules, Phenothiazines
in
Acta Physiologica Scandinavica
volume
116
issue
2
pages
5 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0020438473
  • pmid:6188323
ISSN
0001-6772
DOI
10.1111/j.1748-1716.1982.tb07119.x
language
English
LU publication?
yes
id
93701bbd-3904-41ee-b62d-33cc74eae721
date added to LUP
2016-12-07 14:41:03
date last changed
2025-01-12 17:07:12
@article{93701bbd-3904-41ee-b62d-33cc74eae721,
  abstract     = {{<p>Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (<sup>3</sup>H) leucine‐labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The polymerization of purified brain tubulin was inhibited by the phenothiazines but unaffected by the dibenzazepines at concentrations which inhibited AXT. Phenothiazines and dibenzazepines are chemically related and known to have a high affinity for calmodulin. The possibility that these drugs interefere with calmodulin regulated processes of importance for AXT will be discussed.</p>}},
  author       = {{EKSTRÖM, Per and KANJE, Martin and EDSTRÖM, Anders}},
  issn         = {{0001-6772}},
  keywords     = {{axonal transport; calmodulin; dibenzazepines; frog sciatic nerve; microtubules; Phenothiazines}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{121--125}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Acta Physiologica Scandinavica}},
  title        = {{Effects of phenothiazines and dibenzazepines on axonal transport and microtubule assembly in vitro}},
  url          = {{http://dx.doi.org/10.1111/j.1748-1716.1982.tb07119.x}},
  doi          = {{10.1111/j.1748-1716.1982.tb07119.x}},
  volume       = {{116}},
  year         = {{1982}},
}