Effects of tacrine, velnacrine (HP029), suronacrine (HP128),and 3,4-diaminopyridine on skeletal neuromusculartransmission in vitro

M.F.M. Braga, A.L. Harvey, E.G. Rowan

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Abstract

The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Tacrine, HP029, and 3,4-diaminopyridine augmented responses of chick biventer cervicis preparations to nerve stimulation, with tacrine and HP029 increasing responses to exogenously applied acetylcholine. HP128 blocked responses to nerve stimulation and to carbachol, but increased responses to acetylcholine. 3. In mouse diaphragm preparations that were partially paralysed by tubocurarine or low calcium solutions, tacrine, HP029, and 3,4-diaminopyridine reversed the twitch block. HP128 deepened the block. 4. In mouse triangularis sterni preparations, tacrine and HP029 prolonged the decay phase of endplate potentials and miniature endplate potentials, but had no effect on quantal content at 36 degrees C; above 10 microM, they reduced endplate potential amplitude. 3,4-Diaminopyridine increased quantal content without affecting the time course of the endplate potentials. HP128 (1-10 microM) had no effect on amplitude or time course of endplate potentials, but reduced their amplitude at higher concentrations. 5. Extracellular recording of nerve terminal currents from triangularis sterni preparations revealed that 3,4-diaminopyridine and HP128 had a selective blocking action on the waveform associated with K+ currents, tacrine reduced and prolonged the K(+)-related waveform, and HP029 had nonselective blocking actions only seen at high concentrations. 6. Tacrine and HP029 behave predominantly as anticholinesterase agents, while HP128 has weaker anticholinesterase actions that are masked by cholinoceptor blockade. Tacrine and HP128, but not HP029, have some blocking actions on K+ currents of mouse motor nerve terminals.
LanguageEnglish
Pages909-915
Number of pages6
JournalBritish Journal of Pharmacology
Volume102
Issue number4
Publication statusPublished - Apr 1991

Fingerprint

Tacrine
Cholinesterase Inhibitors
Acetylcholine
In Vitro Techniques
velnacrine
3,4-diaminopyridine
suronacrine
Tubocurarine
Neuromuscular Junction
Carbachol
Cholinergic Receptors
Diaphragm
Calcium

Keywords

  • tacrine
  • aminopyridines
  • acetylcholine release
  • inhibition of acetylcholinesterase
  • potassium currents
  • nerve action
  • potentials
  • neuromuscular transmission

Cite this

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title = "Effects of tacrine, velnacrine (HP029), suronacrine (HP128),and 3,4-diaminopyridine on skeletal neuromusculartransmission in vitro",
abstract = "The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Tacrine, HP029, and 3,4-diaminopyridine augmented responses of chick biventer cervicis preparations to nerve stimulation, with tacrine and HP029 increasing responses to exogenously applied acetylcholine. HP128 blocked responses to nerve stimulation and to carbachol, but increased responses to acetylcholine. 3. In mouse diaphragm preparations that were partially paralysed by tubocurarine or low calcium solutions, tacrine, HP029, and 3,4-diaminopyridine reversed the twitch block. HP128 deepened the block. 4. In mouse triangularis sterni preparations, tacrine and HP029 prolonged the decay phase of endplate potentials and miniature endplate potentials, but had no effect on quantal content at 36 degrees C; above 10 microM, they reduced endplate potential amplitude. 3,4-Diaminopyridine increased quantal content without affecting the time course of the endplate potentials. HP128 (1-10 microM) had no effect on amplitude or time course of endplate potentials, but reduced their amplitude at higher concentrations. 5. Extracellular recording of nerve terminal currents from triangularis sterni preparations revealed that 3,4-diaminopyridine and HP128 had a selective blocking action on the waveform associated with K+ currents, tacrine reduced and prolonged the K(+)-related waveform, and HP029 had nonselective blocking actions only seen at high concentrations. 6. Tacrine and HP029 behave predominantly as anticholinesterase agents, while HP128 has weaker anticholinesterase actions that are masked by cholinoceptor blockade. Tacrine and HP128, but not HP029, have some blocking actions on K+ currents of mouse motor nerve terminals.",
keywords = "tacrine, aminopyridines, acetylcholine release, inhibition of acetylcholinesterase, potassium currents, nerve action, potentials, neuromuscular transmission",
author = "M.F.M. Braga and A.L. Harvey and E.G. Rowan",
year = "1991",
month = "4",
language = "English",
volume = "102",
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journal = "British Journal of Pharmacology",
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TY - JOUR

T1 - Effects of tacrine, velnacrine (HP029), suronacrine (HP128),and 3,4-diaminopyridine on skeletal neuromusculartransmission in vitro

AU - Braga, M.F.M.

AU - Harvey, A.L.

AU - Rowan, E.G.

PY - 1991/4

Y1 - 1991/4

N2 - The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Tacrine, HP029, and 3,4-diaminopyridine augmented responses of chick biventer cervicis preparations to nerve stimulation, with tacrine and HP029 increasing responses to exogenously applied acetylcholine. HP128 blocked responses to nerve stimulation and to carbachol, but increased responses to acetylcholine. 3. In mouse diaphragm preparations that were partially paralysed by tubocurarine or low calcium solutions, tacrine, HP029, and 3,4-diaminopyridine reversed the twitch block. HP128 deepened the block. 4. In mouse triangularis sterni preparations, tacrine and HP029 prolonged the decay phase of endplate potentials and miniature endplate potentials, but had no effect on quantal content at 36 degrees C; above 10 microM, they reduced endplate potential amplitude. 3,4-Diaminopyridine increased quantal content without affecting the time course of the endplate potentials. HP128 (1-10 microM) had no effect on amplitude or time course of endplate potentials, but reduced their amplitude at higher concentrations. 5. Extracellular recording of nerve terminal currents from triangularis sterni preparations revealed that 3,4-diaminopyridine and HP128 had a selective blocking action on the waveform associated with K+ currents, tacrine reduced and prolonged the K(+)-related waveform, and HP029 had nonselective blocking actions only seen at high concentrations. 6. Tacrine and HP029 behave predominantly as anticholinesterase agents, while HP128 has weaker anticholinesterase actions that are masked by cholinoceptor blockade. Tacrine and HP128, but not HP029, have some blocking actions on K+ currents of mouse motor nerve terminals.

AB - The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Tacrine, HP029, and 3,4-diaminopyridine augmented responses of chick biventer cervicis preparations to nerve stimulation, with tacrine and HP029 increasing responses to exogenously applied acetylcholine. HP128 blocked responses to nerve stimulation and to carbachol, but increased responses to acetylcholine. 3. In mouse diaphragm preparations that were partially paralysed by tubocurarine or low calcium solutions, tacrine, HP029, and 3,4-diaminopyridine reversed the twitch block. HP128 deepened the block. 4. In mouse triangularis sterni preparations, tacrine and HP029 prolonged the decay phase of endplate potentials and miniature endplate potentials, but had no effect on quantal content at 36 degrees C; above 10 microM, they reduced endplate potential amplitude. 3,4-Diaminopyridine increased quantal content without affecting the time course of the endplate potentials. HP128 (1-10 microM) had no effect on amplitude or time course of endplate potentials, but reduced their amplitude at higher concentrations. 5. Extracellular recording of nerve terminal currents from triangularis sterni preparations revealed that 3,4-diaminopyridine and HP128 had a selective blocking action on the waveform associated with K+ currents, tacrine reduced and prolonged the K(+)-related waveform, and HP029 had nonselective blocking actions only seen at high concentrations. 6. Tacrine and HP029 behave predominantly as anticholinesterase agents, while HP128 has weaker anticholinesterase actions that are masked by cholinoceptor blockade. Tacrine and HP128, but not HP029, have some blocking actions on K+ currents of mouse motor nerve terminals.

KW - tacrine

KW - aminopyridines

KW - acetylcholine release

KW - inhibition of acetylcholinesterase

KW - potassium currents

KW - nerve action

KW - potentials

KW - neuromuscular transmission

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917982/

M3 - Article

VL - 102

SP - 909

EP - 915

JO - British Journal of Pharmacology

T2 - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -