Abstract
The quinoline derivatives quinine, its stereoisomer quinidine, and chloroquine may worsen or provoke disorders of neuromuscular transmission. In this study, we investigate effects of these drugs on neuromuscular transmission by conventional microelectrode as well as patch-clamp techniques. At 5 x 10-5 M, quinine, quinidine, and chloroquine reduced the quantal content of the end-plate potential by 37-45%. Between 10-6 and 10-4 M, all 3 drugs progressively decreased the amplitude and decay time constant of miniature end-plate potential (MEPP) and miniature end-plate current (MEPC); at 5 x 10-3 M, the MEPP became undetectable. The effect on the MEPP was not reversed by 1 μg/ml neostigmine. Single-channel patch-clamp analysis of the effects of quinine showed that this agent causes a long-lived open-channel as well as a closed-channel block of AChR. Tests for competitive inhibition or desensitization of the acetylcholine receptor (AChR) by quinine in concentrations that had a marked effect on the MEPC and on single-channel open and closed intervals were negative. Because quinoline drugs adversely affect both presynaptic and postsynaptic aspects of neuromuscular transmission at concentrations close to those employed in clinical practice, they should not be used, or used with caution, in disorders that compromise the safety margin of neuromuscular transmission.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 179-189 |
| Number of pages | 11 |
| Journal | Brain Research |
| Volume | 712 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 18 1996 |
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Keywords
- acetylcholine receptor
- channel block
- chloroquine
- neuromuscular transmission
- patch-clamp analysis
- quinidine
- quinine
- transmitter release
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission. / Sieb, Jörn P.; Milone, Margherita; Engel, Andrew G.
In: Brain Research, Vol. 712, No. 2, 18.03.1996, p. 179-189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission
AU - Sieb, Jörn P.
AU - Milone, Margherita
AU - Engel, Andrew G
PY - 1996/3/18
Y1 - 1996/3/18
N2 - The quinoline derivatives quinine, its stereoisomer quinidine, and chloroquine may worsen or provoke disorders of neuromuscular transmission. In this study, we investigate effects of these drugs on neuromuscular transmission by conventional microelectrode as well as patch-clamp techniques. At 5 x 10-5 M, quinine, quinidine, and chloroquine reduced the quantal content of the end-plate potential by 37-45%. Between 10-6 and 10-4 M, all 3 drugs progressively decreased the amplitude and decay time constant of miniature end-plate potential (MEPP) and miniature end-plate current (MEPC); at 5 x 10-3 M, the MEPP became undetectable. The effect on the MEPP was not reversed by 1 μg/ml neostigmine. Single-channel patch-clamp analysis of the effects of quinine showed that this agent causes a long-lived open-channel as well as a closed-channel block of AChR. Tests for competitive inhibition or desensitization of the acetylcholine receptor (AChR) by quinine in concentrations that had a marked effect on the MEPC and on single-channel open and closed intervals were negative. Because quinoline drugs adversely affect both presynaptic and postsynaptic aspects of neuromuscular transmission at concentrations close to those employed in clinical practice, they should not be used, or used with caution, in disorders that compromise the safety margin of neuromuscular transmission.
AB - The quinoline derivatives quinine, its stereoisomer quinidine, and chloroquine may worsen or provoke disorders of neuromuscular transmission. In this study, we investigate effects of these drugs on neuromuscular transmission by conventional microelectrode as well as patch-clamp techniques. At 5 x 10-5 M, quinine, quinidine, and chloroquine reduced the quantal content of the end-plate potential by 37-45%. Between 10-6 and 10-4 M, all 3 drugs progressively decreased the amplitude and decay time constant of miniature end-plate potential (MEPP) and miniature end-plate current (MEPC); at 5 x 10-3 M, the MEPP became undetectable. The effect on the MEPP was not reversed by 1 μg/ml neostigmine. Single-channel patch-clamp analysis of the effects of quinine showed that this agent causes a long-lived open-channel as well as a closed-channel block of AChR. Tests for competitive inhibition or desensitization of the acetylcholine receptor (AChR) by quinine in concentrations that had a marked effect on the MEPC and on single-channel open and closed intervals were negative. Because quinoline drugs adversely affect both presynaptic and postsynaptic aspects of neuromuscular transmission at concentrations close to those employed in clinical practice, they should not be used, or used with caution, in disorders that compromise the safety margin of neuromuscular transmission.
KW - acetylcholine receptor
KW - channel block
KW - chloroquine
KW - neuromuscular transmission
KW - patch-clamp analysis
KW - quinidine
KW - quinine
KW - transmitter release
UR - http://www.scopus.com/inward/record.url?scp=0029868615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029868615&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(95)01349-0
DO - 10.1016/0006-8993(95)01349-0
M3 - Article
C2 - 8814892
AN - SCOPUS:0029868615
VL - 712
SP - 179
EP - 189
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -