Comparative Veterinary Psychopharmacology in Dogs and Cats: Neurotransmitter Targets, Translational Boundaries, and Species-Specific Pharmacokinetics

Behavioral disorders in companion animals are increasingly being managed with pharmacotherapy. However, prescription practices often rely on extrapolation from human psychiatry without considering species-specific phenotypes, diagnostic frameworks, or pharmacokinetic variability. A structured translational approach is required to align mechanistic plausibility with clinical evidence and interspecies constraints. This review consolidates the current information on the pharmacological modulation of neurotransmitter systems in canine and feline behavioral disorders using a comparative framework. Neurotransmitter circuits are mapped to relevant phenotypes. Controlled clinical evidence supports the use of selected serotonergic agents for specific chronic behavioral indications in dogs, whereas evidence in cats remains scarce and indication-specific. Controlled veterinary evidence is also available for selected agents used in acute or situational behavioral indications and for selegiline in canine cognitive dysfunction. Contrastingly, the broader neurotransmitter–phenotype relationships and emerging pharmacological targets discussed in this review are supported by mechanistic or translational evidence and should not be interpreted as established clinical indications. Cross-species translation is most defensible at the level of conserved receptors and transporters, whereas direct transfer of human diagnostic categories and subjective symptoms is limited in veterinary patients. Species- and drug-specific pharmacokinetic differences, along with limited feline data, necessitate careful dose initiation, titration, and monitoring to mitigate adverse effects and drug interactions. This review provides a structured framework for interpreting psychopharmacological evidence in dogs and cats by integrating pharmacological mechanisms, the design and scope of available clinical studies, translational boundaries, and species- and drug-specific pharmacokinetic considerations. Future research could benefit from standardized outcome measures, expanded feline trials, and pragmatic real-world designs.