T-588 protects motor neuron death following axotomy

Neurochem Res. 2004 Feb;29(2):403-6. doi: 10.1023/b:nere.0000013744.57398.fd.

Abstract

R(-)-1-(benzo [b] thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy] ethanol hydrochloride) (T-588) enhances acetylcholine release. This compound slows the motor deterioration of wobbler mouse motor neuron disease and enhances neurite outgrowth and choline acetyltransferase activity in cultured rat spinal motor neurons. We examined the ability of T-588 on axotomized spinal motor neuron death in the rat spinal cord. After the postnatal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of T-588 for 14 consecutive days rescued spinal motor neuron death. Our results showing in vivo neurotrophic activity of T-588 for motor neurons support the applicability of T-588 for the treatment of motor neuron diseases, such as amyotrophic lateral sclerosis and motor neuropathies.

MeSH terms

  • Animals
  • Animals, Newborn
  • Axotomy*
  • Cell Survival / drug effects
  • Denervation
  • Diethylamines / administration & dosage
  • Diethylamines / pharmacology*
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Lumbar Vertebrae
  • Motor Neurons / drug effects*
  • Motor Neurons / physiology*
  • Nerve Growth Factors / administration & dosage
  • Nerve Growth Factors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Thiophenes / administration & dosage
  • Thiophenes / pharmacology*

Substances

  • Diethylamines
  • Nerve Growth Factors
  • Thiophenes
  • T 588