The most commonly encountered centrally acting muscle relaxants for human use include baclofen, carisoprodol, cyclobenzaprine, methocarbamol, and tizanidine. All of these drugs produce some amount of CNS depression in animals. Baclofen has a very narrow margin of safety, and ingestions often necessitate longterm care.
Consultation with an animal poison control center is recommended for any ingestion of baclofen and for large ingestions of other skeletal muscle relaxants.
Baclofen Toxicosis in Animals
Baclofen is a centrally acting skeletal muscle relaxant used in humans to control pain and spasticity from multiple sclerosis, spinal cord injuries, and cord disease. There are no approved veterinary formulations of baclofen; however, it has been used in an extra-label manner to treat some spasticity-related conditions in dogs.
Baclofen is a gamma-aminobutyric acid (GABA) agonist that acts in the brain and spinal cord to inhibit the release of excitatory neurotransmitters. Baclofen in dogs is rapidly absorbed from the GI tract: peak concentrations are reached in approximately 2 hours.
Baclofen is widely distributed, metabolized in the liver, and eliminated primarily in the urine. The half-life in dogs is 3.3–3.6 hours.
Ingestions of 1.3 mg/kg of baclofen have resulted in clinical signs in dogs, and doses of 8 mg/kg have led to death. Clinical signs of baclofen toxicosis have occurred in cats ingesting 1.7 mg/kg.
Clinical signs of baclofen toxicosis generally develop rapidly, occurring within minutes of ingestion; however, onset may be delayed up to a few hours. The most common signs are prolonged vocalization, salivation, vomiting, ataxia, weakness, disorientation, shaking, flaccid paralysis, seizures, and hypothermia or hyperthermia.
Cardiovascular changes such as bradycardia or tachycardia, hypotension or hypertension, and cardiac arrhythmias occur with larger ingestions. Life-threatening clinical signs include dyspnea, nonresponsive seizures, respiratory depression, and respiratory arrest.
Treatment
Treatment of baclofen toxicosis is likely to be prolonged, and early consultation with an animal poison control center is often needed for a positive outcome. The various clinical signs can be treated as follows:
Induction of emesis, followed by administration of a single dose of activated charcoal with a cathartic, should be the course of action in a clinically normal animal if the exposure is very recent.
An alternative to emesis and charcoal is gastric lavage using a cuffed tube to protect the airway; however, strict attention needs to be paid to anesthesia because CNS depression may already be profound.
IV fluids are necessary to correct losses from vomiting and to enhance elimination.
Cyproheptadine (in dogs: 1.1 mg/kg, PO or rectally, every 1–6 hours to effect; in cats: 2–4 mg/cat, PO or rectally, administered every 4–6 hours to effect) is an effective drug for decreasing dysphoria (vocalization, disorientation).
Maropitant (1 mg/kg, SC, IV, or PO, every 24 hours) or ondansetron (0.5–1 mg/kg, IV or PO, every 12 hours) is recommended to prevent and treat vomiting.
Seizures should be treated with the lowest effective dose of diazepam (0.5–1 mg/kg, IV, to effect) or another benzodiazepine; long-acting barbiturates are not recommended, because they result in respiratory depression. Propofol or the careful use of general anesthesia may be necessary for refractory seizures.
Bradycardia is generally responsive to atropine (0.02–0.04 mg/kg, IM, IV, or SC, once).
Hemodialysis and hemoperfusion have been used to treat large overdoses.
IV lipid emulsion has been reported as a successful treatment for some baclofen ingestions. There are several different protocols; most typically, 1.5 mL/kg of a 20% emulsion is administered IV over 5–15 minutes, followed by a CRI of 0.25 mL/kg/minute over 1–2 hours. This sequence can be repeated if clinical signs of toxicosis return and the serum is not lipemic.
Animals with baclofen toxicosis should be monitored and treated for cardiac and respiratory changes and for hypothermia. Ventilatory support may be required in severe cases. The use of flumazenil is controversial and not recommended, because it may precipitate seizures.
Carisoprodol Toxicosis in Animals
Carisoprodol is a drug less commonly used in humans for discomfort associated with painful skeletal muscle conditions. It does not act directly on skeletal muscle; rather, it interrupts neuronal communication within the spinal cord and the descending reticular formation in the brain. No approved veterinary products contain carisoprodol.
Some of the effects of carisoprodol are related to its ability to modulate GABA receptors, and some are due to other mechanisms. In humans, carisoprodol has a very rapid onset of action: clinical signs occur in 30 minutes and last 2–6 hours.
Carisoprodol is metabolized in the liver to several metabolites—including meprobamate, a drug with sedative and anxiolytic effects—and excreted in the urine. The elimination half-life in humans is short for carisoprodol (1.7–2 hours) and long for meprobamate (approximately 10 hours). Little pharmacokinetic information for animals is available.
There is no defined toxic dose of carisoprodol in animals. Clinical signs of toxicosis in dogs include weakness, listlessness, ataxia, abnormal mentation, tachycardia, seizures, and coma.
Treatment
Carisoprodol toxicosis is treated with supportive care, following most of the guidelines provided for baclofen. Hemodialysis and peritoneal dialysis have been used successfully in human intoxications. There are no animal studies. IV lipid emulsion has been used to treat carisoprodol toxicosis in children but has not been evaluated in animals (1).
Cyclobenzaprine Toxicosis in Animals
Cyclobenzaprine is used in humans to relieve muscle spasms associated with acute musculoskeletal disorders. It acts primarily within the CNS at the level of the brainstem. Structurally, cyclobenzaprine is related to some tricyclic antidepressant drugs. No approved veterinary products contain cyclobenzaprine; however, it has been used in an extra-label manner for spasms associated with spinal conditions in dogs.
Cyclobenzaprine is rapidly and almost completely absorbed after being ingested; peak plasma concentrations are reached in 2 hours. It is extensively metabolized in the liver to ten metabolites and excreted in both feces and urine.
There is no defined minimum toxic dose of cyclobenzaprine for animals; however, the following correlations have been reported (2):
Dogs receiving a single oral dose of 2 mg/kg did not develop clinical signs.
Dogs receiving a dosage of 2 mg/kg, PO, every 24 hours for 12 months developed ptyalism, vomiting, and a dry nose and gums.
Dosages of 10 mg/kg every 24 hours for 28 weeks resulted in clinical signs as above, as well as changes in the ECG waveform (prominent P and T waves).
Dosages of 60 mg/kg every 24 hours for 4 weeks led to tachycardia, ataxia, seizures, and death.
Treatment
The various clinical signs of cyclobenzaprine toxicosis can be treated as follows:
Induction of emesis, followed by administration of a single dose of activated charcoal with a cathartic, should be the course of action to treat cyclobenzaprine ingestion in a clinically normal patient if the exposure is very recent.
Gastric lavage using a cuffed tube to protect the airway, followed by administration of a single dose of activated charcoal with a cathartic, is an acceptable alternative.
Cyclobenzaprine undergoes enterohepatic recirculation, so two additional doses of activated charcoal without a cathartic should be administered at intervals of 6–8 hours, while the patient is monitored for hypernatremia.
IV fluids should be administered to correct losses from vomiting.
Seizures are best treated with the lowest effective dose of diazepam (0.25–0.5 mg/kg, IV, to effect) or another benzodiazepine.
Hemodialysis is unlikely to be helpful.
IV fat emulsion has been used successfully in dogs and humans (3).
Further treatment is supportive.
Methocarbamol Toxicosis in Animals
Methocarbamol is a centrally acting skeletal muscle relaxant used in animals to treat a wide variety of disorders associated with muscle inflammation, trauma, and rigidity. The mechanism of action other than CNS depression is unknown.
In cats, methocarbamol has some direct effect on skeletal muscle fibers. Absorption in dogs is rapid: peak plasma concentrations are reached in 2 hours.
Methocarbamol is extensively metabolized in the liver and almost completely excreted in the urine; its elimination half-life is 1.7 hours.
The most common clinical signs of methocarbamol intoxication include lethargy, weakness, ataxia, and vomiting. Large ingestions may result in more severe CNS signs.
Treatment
Treatment of methocarbamol toxicosis consists of supportive care. Induction of emesis, followed by administration of a single dose of activated charcoal with a cathartic, should be the course of action in a clinically normal animal if the exposure was recent. An alternative is gastric lavage using a cuffed tube to protect the airway.
Animals with methocarbamol toxicosis should be monitored frequently for CNS and respiratory depression. Additional treatment depends on the amount of drug ingested and on the specific clinical signs.
Tizanidine Toxicosis in Animals
Tizanidine is an alpha-2-adrenergic agonist used to treat muscle spasticity in humans with multiple sclerosis, spinal cord injury, or other neuromuscular disorders. It enhances presynaptic inhibition, thereby decreasing the release of excitatory neurotransmitters in the spinal cord. Other mechanisms of action are also present in the spinal cord.
Few pharmacokinetic data on tizanidine are available for animals. Absorption in dogs is moderately slow: peak plasma concentrations are reached in 2.25–2.5 hours. Tizanidine undergoes hepatic metabolism, and approximately 80% is excreted in the urine.
Clinical signs of tizanidine toxicosis in dogs and cats include lethargy and sedation, bradycardia, hypotension, ataxia, and vomiting; signs generally occur at doses greater than 0.45 mg/kg.
Treatment
Tizanidine toxicosis is treated with supportive care, largely following the guidelines for baclofen. Pressor agents may be necessary if hypotension is severe and nonresponsive to IV fluids.
Hemodialysis is unlikely to be beneficial in overdoses, because tizanidine has limited water solubility.
IV fat emulsion has been used successfully in humans, but it has not yet been evaluated in animals (4).
Key Points
Common early signs of toxicosis are weakness, ataxia, and lethargy, which can rapidly progress to more serious clinical signs.
Baclofen toxicosis is especially dangerous in small animals. The margin of safety is small and the onset of severe signs very rapid.
IV fat has been used successfully in humans or animals to treat toxicoses due to most of these skeletal muscle relaxants.
For More Information
American Society for the Prevention of Cruelty to Animals (ASPCA)
Hay Kraus BL. Centrally acting muscle relaxants. In Aarnes T, Lerche P, eds. Pharmacology in Veterinary Anesthesia and Analgesia. Wiley; 2024:183-201. doi:10.1002/9781118975169.ch15
Farrell KS. Baclofen. In Hovda LR, Brutlag AG, Poppenga RH, Epstein SE, eds. Blackwell's Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology. 3rd ed. Wiley-Blackwell; 2024: 129-133.
Also see pet health content regarding poisoning from muscle relaxants.
References
Chegondi M, Badheka A, Chacham S, Kahana M. Intravenous lipid emulsion rescue therapy in a child with carisoprodol overdose. Cureus. 2019;11(11):e6250. doi:10.7759/cureus.6250
Cyclobenzaprine product monograph: Cyclobenzaprine (Cyclobenzaprine Hydrochloride), USP, 10 mg Tablets. Sanis Health Inc.; 2017.
Dreese K, Odunayo A, Bucknoff MC. Case report: treatment of cyclobenzaprine ingestion in two dogs with intravenous intralipid therapy. Front Vet Sci. 2024;11:1354028. doi:10.3389/fvets.2024.1354028
Souza R, Jauregui J, Valento M. Mixed propranolol and tizanidine overdose treated with intravenous lipid emulsion. Toxicol Commun. 2018;2(1):71-74. doi:10.1080/24734306.2018.1522027
