Muscle spasticity is a characteristic of many clinical conditions, including trauma, myositis, muscular and ligamentous sprains and strains, intervertebral disk disease, tetanus, strychnine poisoning, neurological disorders, and exertional rhabdomyolysis (see Exertional Myopathies in Horses and Exertional Myopathy in Dogs). An increase in tonic stretch reflexes originates from the CNS with involvement of descending pathways and results in hyperexcitability of motor neurons in the spinal cord.
Central muscle relaxants (sometimes referred to as skeletal muscle relaxants) alleviate muscle spasms by modifying the stretch reflex arc or by interfering with the excitation coupling process in the muscle itself. Centrally acting muscle relaxants block interneuronal pathways in the spinal cord and in the midbrain reticular activating system.
Some central muscle relaxants also have sedative effects, which are beneficial to animals that are anxious or in pain. Hydantoin derivatives have a direct action on muscle.
Methocarbamol as a Central Muscle Relaxant
Methocarbamol is a centrally acting muscle relaxant that is chemically related to guaifenesin; guaifenesin itself is produced as a metabolite of methocarbamol. Its exact mechanism of action is unknown, and it has no direct relaxant effect on striated muscle, nerve fibers, or the motor end plate.
Methocarbamol also has a sedative effect. In dogs, cats, and horses, it is indicated as adjunct therapy for acute inflammatory and traumatic conditions of skeletal muscle and as a means of decreasing muscle spasms.
Because methocarbamol is a CNS depressant, it should not be given with other drugs that depress the CNS. Overdosage is generally characterized by CNS depression; however, emesis (in small animals), salivation, weakness, and ataxia might occur.
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Methocarbamol is metabolized via dealkylation and hydroxylation, followed by conjugation to form glucuronides and sulfates. Only after oral administration of methocarbamol is guaifenesin detectable in equine plasma and urine, indicating that first-pass metabolism is necessary for guaifenesin to be produced as a metabolite.
Because of their sedative effects, methocarbamol and guaifenesin are regulated by equine sports organizations, and withdrawal periods must be respected.
Guaifenesin as a Central Muscle Relaxant
Guaifenesin (glyceryl guaiacolate) is a centrally acting muscle relaxant believed to depress or block nerve impulse transmission at the internuncial neuron (neuron found completely within the CNS) level of subcortical areas of the brain, brainstem, and spinal cord. It also has mild sedative effects.
Historically, guaifenesin was most commonly used as part of general anesthesia for horses and farm animals; however, its use has decreased substantially. Unlike neuromuscular blocking agents, guaifenesin provides relaxation that does not result in paralysis.
To induce muscle relaxation as an adjunct to anesthesia for short procedures in horses and ruminants, guaifenesin is administered at 50–100 mg/kg, IV (1, 2). It relaxes laryngeal and pharyngeal muscles, enabling easier intubation; however, it has little effect on the diaphragm and respiratory function.
Guaifenesin can cause transient increases in cardiac rate and decreases in blood pressure. It has also been used to treat horses with exertional rhabdomyolysis and dogs with strychnine poisoning.
Guaifenesin overdose results in apneustic breathing, nystagmus, hypotension, and contradictory muscle rigidity. Overdosage is treated with supportive care until the drug is cleared to nontoxic levels.
Benzodiazepines as Central Muscle Relaxants
Benzodiazepines, such as diazepam and midazolam, affect polysynaptic reflexes at the supraspinal level, act as a spinal cord depressant at the interneuronal level, and inhibit presynaptic acetylcholine release.
When used for muscle relaxation benzodiazepines are administered as an adjunct to anesthesia, in the management of clinical signs of tetanus, and in the treatment of functional urethral obstruction and urethral sphincter hypertonus in cats.
Baclofen as a Central Muscle Relaxant
Baclofen is a central muscle relaxant used to control spasticity and pain in humans with multiple sclerosis and spinal cord disorders.
Baclofen is structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It acts as a GABA receptor B agonist to decrease calcium influx into presynaptic nerve terminals, thereby decreasing the amount of excitatory neurotransmitters released by primary afferent neurons in the spinal cord and brain. This action results in decreased muscle tone, as well as pain associated with spasticity.
Because it has a very narrow safety margin, baclofen is not recommended for use in veterinary medicine. Rarely, it has been administered to treat dogs with tetanus and to decrease urethral resistance in the treatment of urinary retention (3). Even at doses as low as 1.3 mg/kg, PO, dogs can have clinical signs of vomiting, depression, and vocalization (4). In cases of overdosage, the severity of CNS signs can be substantial and can include dysphoria, lateral recumbency, or coma.
Treatment for baclofen toxicosis should include rapid and aggressive decontamination and intensive supportive care. Affected dogs might require positive-pressure ventilation to treat the severe obtundation, respiratory depression, and respiratory arrest or hypoventilation that can result from baclofen toxicosis.
Cyproheptadine, a serotonin antagonist, may be administered orally or rectally as needed to decrease vocalization or disorientation due to baclofen toxicosis. IV lipid emulsion has been useful to treat some dogs with baclofen toxicosis.
Dantrolene as a Central Muscle Relaxant
Dantrolene, a hydantoin derivative, is structurally and pharmacologically different from other central muscle relaxants. Unlike the centrally acting agents described above, dantrolene has a direct action on muscle, likely by interfering with the release of calcium from the sarcoplasmic reticulum. It has no discernible effects on respiratory and cardiac function but can cause dizziness and sedation.
Dantrolene is used to treat malignant hyperthermia in various species, porcine stress syndrome, equine postanesthetic myositis, and equine exertional rhabdomyolysis.
Because of its sedative effects, dantrolene is regulated by equine sports organizations, and withdrawal periods must be respected.
For More Information
Also see pet owner content regarding drugs used to treat bone and muscle disorders.
References
Brosnan RJ, Steffey EP, Escobar A, Palazoglu M, Fiehn O. Anesthetic induction with guaifenesin and propofol in adult horses. Am J Vet Res. 2011;72(12):1569-1575. doi:10.2460/ajvr.72.12.1569
Abrahamsen EJ. Ruminant field anesthesia. Vet Clin North Am Food Anim Pract. 2008;24(3):429-441. doi:10.1016/j.cvfa.2008.07.001
Lane I. Urinary obstruction and functional urine retention. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. 6th ed. WB Saunders; 2000:93-96.
Khorzad R, Lee JA, Whelan M, et al. Baclofen toxicosis in dogs and cats: 145 cases (2004–2010). J Am Vet Med Assoc. 2012;241(8):1059-1064. doi:10.2460/javma.241.8.1059
