Attenuation of motor nerve terminal repetitive discharge by the 21- aminosteroid tirilazad: Evidence of a neural calcium antagonist action

E. D. Hall, P. A. Yonkers

Research output: Contribution to journalArticlepeer-review


Pretreatment with the 21-aminosteroid antioxidant compound tirilazad mesylate has been previously shown to retard the axotomy-induced anterograde degeneration of soleus motor nerve terminals in the cat. In the present study, we examined tirilazad's effects (7.7, 13.0 or 30.0 mg/kg twice daily P.O. for 6 days) on the excitability of normal cat soleus motor nerve terminals. Low frequency (0.4 Hz) neuromuscular transmission was measured as well as the occurrence of muscle contractile potentiation in response to either a 400 Hz/10 s episode of tetanic conditioning stimulation of the soleus nerve or the administration of a 200 μg/kg i.v. dose of the neuromuscular facilitatory drug edrophonium. The mechanism of the post- tetanic potentiation (PTP) or edrophonium-induced facilitatory response involves the occurrence of a stimulus-dependent repetitive discharge of the soleus motor nerve terminals due to an exaggeration of the nerve terminal Ca2+-mediated after-depolarization. Tirilazad pretreatment caused a dose- related suppression of PTP and the edrophonium response indicative of a suppression of motor nerve terminal repetitive discharge. These effects were not shared by 6 days of oral pretreatment of cats with a high dose combination of the antioxidants vitamin E (200 I.U./day) and selenium (50 μg/day). Thus, it is unlikely that the antioxidant properties of tirilazad are involved in the suppression of motor nerve terminal excitability. Rather, it is proposed that tirilazad suppresses delayed motor nerve terminal Ca2+ conductances secondary to its ability to decrease membrane phospholipid fluidity, and that this action might in some circumstances contribute to its neuroprotective activity.

Original languageEnglish
Pages (from-to)346-349
Number of pages4
JournalBrain Research
Issue number1-2
StatePublished - Jan 1 1998


  • Cat
  • Edrophonium
  • Motor nerve terminal
  • Post-tetanic potentiation
  • Repetitive discharge
  • Soleus
  • Tirilazad

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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