BUSPIRONE HCL

Chemistry - An arylpiperazine derivative anxiolytic agent, buspirone HCl differs structurally fromthe benzodiazepines. It occurs as a white, crystalline powder with solubilities at 25°C of 865 mg/mlin water and about 20 mg/ml in alcohol.

Storage, Stability, Compatibility

Buspirone HCl tablets should be stored in tight, light-resistantcontainers at room temperature. After manufacture, buspirone tablets have an expiration date of 36months.

Pharmacology - BUSPIRONE HCL

Buspirone is an anxioselective agent. Unlike the benzodiazepines, buspirone doesnot possess any anticonvulsant or muscle relaxant activity and little sedative or psychomotorimpairment activity. The mechanism for buspirone's anxiolytic action is not well understood, but itdoes not appear to share the same mechanisms as the benzodiazepines (does not have significantaffinity for benzodiazepine receptors and does not affect GABA binding). Buspirone has a highaffinity for serotonin receptors in the CNS, but the role it plays is not well understood. Buspironeappears to have mixed agonist/antagonist properties on dopaminergic receptors.

Uses, Indications

Buspirone may be effective in treating certain behavior disorders in dogs andcats; principally those that are fear/phobia related.

Pharmacokinetics - BUSPIRONE HCL

In humans, buspirone is rapidly and completely absorbed, but a high firstpass effect limits systemic bioavailability to approximately 5%. Binding to plasma proteins is veryhigh (95%). In rats, highest tissue concentrations are found in the lungs, kidneys, and fat. Lowerlevels are found in the brain, heart, skeletal muscle, plasma and liver. Both buspirone and itsmetabolites are distributed into maternal milk. The elimination half-life (in humans) is about 2-4hours. Buspirone is hepatically metabolized to several metabolites (including one that is active: 1-
PP). These metabolites are excreted primarily in the urine.

Contraindications, Precautions, Reproductive Safety

Buspirone should be used with cautionwith either significant renal or hepatic disease. While buspirone has far less sedating propertiesthan many other like drugs, it should potentially be used in caution in working dogs. While thedrug has not been proven to be safe during pregnancy, doses of up to 30 times the labeled dosagein rabbits and rats demonstrated no teratogenic effects.

Adverse Effects, Warnings

Adverse effects are usually minimal with buspirone and it is generally well tolerated. The most likely adverse effect profile seen with buspirone includes dizziness, headache, nausea/anorexia, and restlessness. Other neurologic effects (including sedation) may benoted. Rarely, tachycardias and other cardiovascular symptoms may be present.

Overdosage, Acute Toxicity

Limited information is available. The oral LD50 in dogs is: 586mg/kg. Oral overdoses may produce vomiting, dizziness, drowsiness, miosis and gastric distention.
Standard overdose protocols should be followed after ingestion has been determined.

Drug Interactions

Food may decrease the rate of absorption, but reduce the first passmetabolism of the drug with a net increase in area under the curve. The clinical significance of thisinteraction is not thought to be significant and the manufacturer recommends dosing without regardto food. Use of monoamine oxidase inhibitors (rarely used in veterinary medicine), includingfurazolidone, with use of buspirone is not recommended because dangerous hypertension mayoccur.