Naltrexone
Naltrexone is a synthetic, long-acting **pure opioid antagonist**. While structurally similar to naloxone, it has significantly higher oral bioavailability and a longer duration of action. In veterinary medicine, it is primarily utilized off-label as an adjunctive treatment for **compulsive behavior disorders**, such as: - Acral lick dermatitis (lick granulomas) - Tail chasing - Flank sucking - Other self-mutilating or stereotypic behaviors **Clinical Pearl**: The rationale for its use in behavior medicine stems from the hypothesis that stereotypic behaviors stimulate the release of endogenous opioids (endorphins), which reinforce the behavior. By blocking these receptors, naltrexone removes the internal "reward," helping to extinguish the compulsive action.
Mechanism: Naltrexone acts as a **competitive antagonist** at opioid receptors, with the highest affinity for **μ (mu)** receptors, followed by **κ (kappa)** and **δ (delta)** receptors. - **Mechanism in Behavior Disorders**: Compulsive behaviors → Release of endogenous endorphins → Binding to μ-receptors → Reinforcement/Analgesia. - Naltrexone **blocks** these receptors → Prevents endorphin binding → Eliminates the auto-reinforcing reward loop of the stereotypic behavior.
Dosing by species
- As adjunctive therapy in behavior disorders · 25-50 mg/cat · PO · q24h · Note: has a bitter taste
- As adjunctive therapy in behavior disorders (tail chasing or excessive licking) · 1-2 mg/kg · PO · daily · Long-term therapy may be required · First give 0.01 mg/kg SC of naloxone to determine if narcotic antagonists may be effective, if so give naltrexone.
- As adjunctive therapy in behavior disorders · 2-5 mg/kg · PO · once daily
- As adjunctive therapy in behavior disorders · 1-2.2 mg/kg · PO · q8-12h
- For the adjunctive treatment of acral pruritic dermatitis · 2.2 mg/kg · PO · once daily · one-month trial · Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited. Expense is of concern.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Adverse effects
- Drowsiness
- Minor changes in behavior
- Elevated hepatic enzymes (AST, ALT)
Drug interactions
- Opioid partial-agonists (e.g., butorphanol, pentazocine, nalbuphine) · May antagonize the effects of these agents, including respiratory depression and analgesia.
- Clonidine · Naltrexone may reduce the hypotensive and bradycardic effects of clonidine.
- Yohimbine · Naltrexone may increase the CNS effects of yohimbine (anxiety, tremors, nausea, palpitations) and increase plasma cortisol levels.
Monitoring
- Clinical efficacy (reduction in stereotypic behaviors)
- Liver enzymes (AST, ALT) if using very high doses with prolonged therapy
Overdose
Specific overdosage information is not provided in the monograph. However, as an opioid antagonist, massive overdoses could theoretically cause dysphoria or precipitate withdrawal in opioid-dependent patients. Monitor liver enzymes if very high doses are ingested.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.