VPT 321: Veterinary Neuropharmacology (2+1) copy 1

Central and direct acting muscle relaxants

CENTRAL AND DIRECT MUSCLE RELAXANTS

Central and direct acting muscle relaxants are:

• Chemically and pharmacologically different from neuromuscular blockers.
• Does not affect neuromuscular transmission or EPP but uncouples contraction from depolariztion of the muscle membrane.
• Depolarization triggered release of calcium ions from sarcoplasmic reticulum is reduced.
• Fast contracting twitch muscles are affected than slow contracting.
• Reduce skeletal muscle tone by a selective action in the cerebrospinal axis, without altering conciousness.
• Do not have sedative action.
• Have no effect on neuromuscular transmission and on muscle fibres.
  Reduce rigidity,spasticity and hyperreflexia.

Difference between central and peripherally acting muscle relaxants

Centrally acting muscle relaxants	Peripherally acting muscle relaxants
Muscle tone decreased No reduction in voluntary movements	Muscle paralysis Voluntary movements are lost
Postsynaptic reflexes in CNS are inhibited	Neuromuscular transmission is blocked
CNS depression	CNS effect not significant
Administred orally/parentrally	Administered by i.v.only
Value in the treatment of spastic muscle spasms, tetanus	Commonly used for short procedures

Dantrolene a centrally acting muscle relaxant is

• Absorbed orally
• Penetrates BBB and produces sedation
• Metabolized by liver and excreted by kidney
• Reduces spasticity  upper motor neurones disorders
• Drug of choice for malignant hyperthermia due to persistent release of calcium ions from Sarcoplasmic reticulum. (induced by fluorinated anaesthetics and Ach in genetically susceptible individuals)

Adverse effects

• Muscle weakness
• Sedation
• Malaise
• Light headedness and other central effects.

Other centrally acting muscle relaxants are:

• Mephenesin group: Mephenesin, Carisoprodol, Chlorzoxazone, Chlormerzanone,Methocarbamol
• Benzodiazepines: Diazepam
• GABA derivatives: Baclofen.

Mephenesin is also known as internuncial neurone blocking agent because of its primary action in the spinal intenuncial neurone which modulate reflexes maintaining muscle tone.