Skip to main content
SpringerLink
Log in

Intrathecal Injection of Antispastic Drugs in Rats: Muscle Relaxant Action of Midazolam, Baclofen, 2-Aminophosphonoheptanoic Acid (AP7) and Tizanidine

  • Conference paper
Local-spinal Therapy of Spasticity

Abstract

Spasticity has been defined as a motor disorder characterized by a velocity-sensitive increase in the resistance to passive stretch of muscles, accompanied by exaggerated tendon reflexes. This is thought to result from the hyperexcitability of stretch reflexes as one component of the upper motor neurone syndrome [9, 51]. This definition does not, however, apply to all symptoms and complaints of the upper motor neurone syndrome, for example exaggerated flexor reflexes (flexor spasms), muscle weakness and loss of dexterity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anden N-E, Corrodi H, Fuxe K, Hökfelt T, Rydin C, Svensson T (1970) Evidence for a central noradrenaline receptor stimulation by Clonidine. Life Sci 9:513–523

    Article  PubMed  CAS  Google Scholar 

  2. Bowery NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnball MJ (1984) Gaba receptor multiplicity. Neuropharmacology 23:219–231

    Article  PubMed  CAS  Google Scholar 

  3. Chen D-F, Bianchetti M, Wiesendanger M (1986) Modulation of flexor reflexes in rats by a noradrenergic agonist and antagonists. Neurosci Lett 26 [Suppl]: S162

    Google Scholar 

  4. Cook JB, Nathan PW (1967) On the site of action of diazepam in spasticity in man. J Neurol Sci 5:33–37

    Article  PubMed  CAS  Google Scholar 

  5. Costa E, Guidoni A (1979) Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol 19:531–545

    Article  PubMed  CAS  Google Scholar 

  6. Coward DM, Davies J, Herrling P, Rüdeberg C (1984) Pharmacological properties of tizanidine (DS 103-282). In: Conrad B, Benecke R, Bauer HJ (eds) Die klinische Wertung der Spastik. Schattauer, Stuttgart, pp 61–69

    Google Scholar 

  7. Curtis DR, Duggan AW, Felix D, Johnston GAR (1970) GABA, bicuculline and central inhibition. Nature 226:1222–1224

    Article  PubMed  CAS  Google Scholar 

  8. Curtis DR, Lodge D, Bornstein JC, Peer MJ (1981) Selecive effects of (-)baclofen on spinal synaptic transmission in the cat. Exp Brain Res 42:158–170

    Article  PubMed  CAS  Google Scholar 

  9. Davidoff RA (1985) Antispasticity drugs: Mechanisms of action. Ann Neurol 17:107–116

    Article  PubMed  CAS  Google Scholar 

  10. Davidoff RA, Hackman JC (1984) Spinal inhibition. In: Davidoff RA (ed) Handbook of the Spinal Cord, vols II and III. Anatomy and Physiology. Dekker, New York, pp 385–459

    Google Scholar 

  11. Davies J, Evans RH, Herrling PL, Jones AW, Olvermann HJ, Pook P, Watkins JC (1986) CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for (3H) D-AP5 binding sites on brain membranes and anticonvulsant activity. Brain Res 382:169–173

    Article  PubMed  CAS  Google Scholar 

  12. Davies J, Johnston SE, Hill DR, Quinlan JE (1984) Tizanidine (DS 103-282), a centrally acting muscle relaxant, selectively depresses excitation of feline dorsal horn neurones to noxious peripheral stimuly by an action at a 2-adrenoceptors. Neurosci Lett 48:197–202

    Article  PubMed  CAS  Google Scholar 

  13. Davies J, Watkins JC (1983) Role of excitatory amino acid receptors in mono-and polysynaptic excitation in the cat spinal cord. Exp Brain Res 4:280–290

    Google Scholar 

  14. Doxey JC, Smith CFC, Walker JM (1977) Selectivity of blocking agents for pre-and postsynaptic β-adrenoceptors. Br J Pharmacol 60:91–96

    PubMed  CAS  Google Scholar 

  15. Dralle D, Müller H, Zierski J, Klug N (1985) Intrathecal baclofen for spasticity. Lancet 2:1003

    Article  PubMed  CAS  Google Scholar 

  16. Hassan N, McLellan DL (1980) Double-blind comparison of single doses of DS 103-282, baclofen and placebo for suppression of spasticity. J Neurol Neurosurg Psychiatry 43:1132–1136

    Article  PubMed  CAS  Google Scholar 

  17. Haefely W, Pieri L, Polc P, Schaffner R (1981) General pharmacology and neuropharmacology of benzodiazepine derivatives. In: Hoffmeister F, Stille G (eds) Handbook of Experimental Pharmacology, vol 55/II. Psychotropic Agents. Springer, Berlin Heidelberg New York, pp 13–262

    Google Scholar 

  18. Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516

    Article  PubMed  CAS  Google Scholar 

  19. Kameyama T, Nabeshima T, Matsuno K, Sugimoto A (1986) Comparison of α-adreno-ceptor involvement in the antinociceptive action of tizanidine and Clonidine in the mouse. Eur J Pharmacol 125:257–264

    Article  PubMed  CAS  Google Scholar 

  20. Kehne JH, Gallager DW, Davis M (1985) Spinalization unmasks clonidine’s a 1-adrenergic mediated excitation of the flexor reflex in rats. J Neurosci 5:1583–1590

    PubMed  CAS  Google Scholar 

  21. Kroin JS, Penn RD, Beissinger RL, Arzbaecher RC (1984) Reduced spinal reflexes following intrathecal baclofen in the rabbit. Exp Brain Res 54:191–194

    Article  PubMed  CAS  Google Scholar 

  22. Marshall KC (1983) Catecholamines and their action in the spinal cord. In: Davidoff RA (ed) Handbook of the Spinal Cord, vol I. Pharmacology. Dekker, New York, pp 275–328

    Google Scholar 

  23. Müller H, Börner U, Zierski J, Hempelmann G (1986) Intrathecal baclofen in tetanus. Lancet 1:317–318

    Article  PubMed  Google Scholar 

  24. Müller H, Gerlach H, Boldt J, Börner U, Hild P, Oehler KU, Zierski J, Hempelmann G (1986) Spastik-Behandlung mit rückenmarksnaher Gabe von Morphin oder Midazolam. Anaesthesist 35:306–316

    PubMed  Google Scholar 

  25. Muhyaddin M, Roberts PJ, Woodruff GN (1983) Presynaptic γ-aminobutyric acid receptors in the rat anococcygeus muscle and their antagonism by 5-aminovaleric acid. Br J Pharmacol 77:163–168

    Google Scholar 

  26. Newberry NR, Nicoli RA (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308:450–452

    Article  PubMed  CAS  Google Scholar 

  27. Newman PM, Nogues M, Newman PK, Weightman D, Hudgson P (1982) Tizanidine in the treatment of spasticity. Eur J Clin Pharmacol 23:31–35

    Article  PubMed  CAS  Google Scholar 

  28. Nistri A (1983) Spinal cord pharmacology of GABA and chemically related amino acids. In: Davidoff RA (ed) Handbook of the Spinal Cord, vol I. Pharmacology. Dekker, New York, pp 45–104

    Google Scholar 

  29. Peet MJ, Leah JD, Curtis DR (1983) Antagonists of synaptic and amino acid excitation of neurones in the cat spinal cord. Brain Res 226:83–95

    Article  Google Scholar 

  30. Penn RD, Kroin JS (1984) Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1:1078

    Article  PubMed  CAS  Google Scholar 

  31. Penn RD, Kroin JS (1985) Continuous intrathecal baclofen for severe spasticity. Lancet 2:125–127

    Article  PubMed  CAS  Google Scholar 

  32. Pierau FK, Zimmermann P (1973) Action of a GABA-derivative on post-synaptic potentials and membrane properties of cats’ spinal motoneurones. Brain Res 54:376–380

    Article  PubMed  CAS  Google Scholar 

  33. Pieri L, Schaffner R, Scherschlicht R, Polc P, Sepinwall J, Davidson A, Möhler H, Cumin R, Da Prada M, Burkhard WP, Keller HH, Müller RKM, Gerold M, Pieri M, Cook L, Haefly W (1981) Pharmacology of midazolam. Drug Res 31:2180–2198

    CAS  Google Scholar 

  34. Pittermann W, Sontag K-H, Wand P, Rapp K, Deerberg F (1976) Spontaneous occurrence of spastic paresis in Han-Wistar rats. Neurosci Lett 2:45–49

    Article  PubMed  CAS  Google Scholar 

  35. Polc P (1985) 2-Amino-7-phosphono-heptanoic acid depresses γ-motoneurons and polysynaptic reflexes in the cat spinal cord. Eur J Pharmacol 117:385–389

    Article  Google Scholar 

  36. Polc P, Haefely W (1982) Benzodiazepines enhance the bicuculline-sensitive part of recurrent Renshaw inhibition in the cat spinal cord. Neurosci Lett 28:193–197

    Article  PubMed  CAS  Google Scholar 

  37. Potashner SJ (1979) Baclofen: effects on amino acid release and metabolism in slices of guina-pig cerebral cortex. J Neurochem 32:103–109

    Article  PubMed  CAS  Google Scholar 

  38. Romijn JA, van Lieshout JJ, Velis DN (1986) Reversible coma due to intrathecal baclofen. Lancet 2:696

    Article  PubMed  CAS  Google Scholar 

  39. Sayers AC, Bürki HR, Eichenberger E (1980) The pharmacology of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (DS 103-282), a novel myotonolytic agent. Drug Res 30:793–803

    CAS  Google Scholar 

  40. Schmidt RF, Vogel ME, Zimmermann M (1967) Die Wirkung von Diazepam auf die präsynaptische Hemmung und andere Rükkenmarksreflexe. Naunyn Schmiedebergs Arch Pharmacol 258:69–82

    CAS  Google Scholar 

  41. Schwarz M, Klockgether T, Turski L, Sontag K-H (1986) δ-Aminovaleric acid antagonizes muscle relaxant action of baclofen in the spinal cord. Naunyn Schmiedebergs Arch Pharmacol 334: R51

    Google Scholar 

  42. Schwarz M, Turski L, Sontag K-H (1984) CGS 8216, Ro 15-1788 and methyl-β carboline-3-carboxylate, but not EMD 41717 antagonize the muscle relaxant effects of diazepam in genetically spastic rats. Life Sci 35:1415–1421

    Article  Google Scholar 

  43. Turski L, Klockgether T, Sontag K-H, Herrling P, Watkins JC (1987) Muscle relaxant and anticonvulsant activity of 3-([-]2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid, a novel N-methyl-D-aspartate antogonist in rodents. Neurosci Lett 73:143–148

    Article  PubMed  CAS  Google Scholar 

  44. Turski L, Schwarz M, Klockgether T, Sontag K-H (1986) Substantia nigra and endopeduncular nucleus: supraspinal sites of the muscle relaxant action of tizanidine. Brain Res 379:367–371

    Article  PubMed  CAS  Google Scholar 

  45. Turski L, Schwarz M, Turski WA, Klockgether T, Sontag K-H, Collins JF (1985) Muscle relaxant action of excitatory amino acid antagonists. Neurosci Lett 53:321–326

    Article  PubMed  CAS  Google Scholar 

  46. Watkins JC (1984) Excitatory amino acids and central synaptic transmission. Trends Pharmacol Sci 5:373–376

    Article  CAS  Google Scholar 

  47. Wiesendanger M, Chapman CE, Macpherson J, Berger W (1984) Neurophysiological investigations of tizanidine. In: Conrad B, Benecke R, Bauer HJ (eds) Die klinische Wertung der Spastizität. Schattauer, Stuttgart, pp 39–55

    Google Scholar 

  48. Wilson PR, Yaksh TL (1978) Baclofen is antinociceptive in the spinal intrathecal space of animals. Eur J Pharmacol 51:323–330

    Article  PubMed  CAS  Google Scholar 

  49. Wüllner U, Klockgether T, Schwarz M, Sontag K-H (1987) Behavioural actions of baclofen in the rat ventromedial thalamic nucleus: antagonism by δ-aminovalerate. Brain Res (in press)

    Google Scholar 

  50. Yaksh TL, Rudy TA (1976) Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 17:1031–1036

    Article  PubMed  CAS  Google Scholar 

  51. Young PR, Delwaide PJ (1981) Drug therapy, Spasticity. N Engl J Med 304:28–33, 96–99

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. M. Schwarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Klockgether
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Turski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K.-H. Sontag
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept. Anesthesiology and Intensive Care Medicine, Justus-Liebig-University, Klinikstr. 29, D-6300, Gießen, Germany

    Hermann Müller MD

  2. Dept. Neurosurgery, Justus-Liebig-University, Klinikstr. 29, D-6300, Gießen, Germany

    Jan Zierski MD

  3. Dept. Neurosurgery, Rush-Presbyterian-St. Luke’s Medical Center Rush Medical College, 1753 West Congress Parkway, Chicago, Illinois, 60612, USA

    Richard D. Penn MD

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Schwarz, M., Klockgether, T., Turski, L., Sontag, KH. (1988). Intrathecal Injection of Antispastic Drugs in Rats: Muscle Relaxant Action of Midazolam, Baclofen, 2-Aminophosphonoheptanoic Acid (AP7) and Tizanidine. In: Müller, H., Zierski, J., Penn, R.D. (eds) Local-spinal Therapy of Spasticity. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-72954-6_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-72954-6_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-18295-5

  • Online ISBN: 978-3-642-72954-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation