Buspirone: Pharmacokinetics,side effects and mechanism of action

An anti-anxiety drug

Buspirone, also known as Buspa, and Hisblon, is a new generation of non-BZ anxiolytic drug with anti-anxiety effects and a different mechanism of action from that of benzodiazepines. It mainly acts on the 5HT1A receptor and dopamine receptor in the hippocampus, which makes the serotonin function down-regulate and produces an anxiolytic effect. It is a highly selective anxiolytic drug with affinity for dopamine receptors, and blocks synapses. The dopamine receptor of the anterior membrane has an antidepressant effect due to its ability to reduce the sensitivity of serotonin receptors in the body, and can reverse the tonicity by inhibiting γ-aminobutyric acid, which may affect other midbrain effects and nerve transmission system. It has an anti-anxiety activity but no hypnosis, muscle relaxation and anticonvulsant effects. It is not suitable for acute cases due to its slow onset of action. Buspirone can also be used for anxiety with mild depression. Its biggest advantage is that Buspirone does not carry the risk of physical dependence, so there is no risk of abuse.

With the aspect of therapeutic dose, buspirone has a lesser sedative effect than that of benzodiazepines. In addition, there is no evidence of physical or psychological dependence or reports of withdrawal symptoms. It is not considered as a drug-of-abuse even if it is taken by people with greater drug dependence. It is not a member of the controlled drugs.

Buspirone is approved in the United Statesby the Food and Drug Administration (FDA) for treatment of anxiety disorders or can also be used for the short-term relief of the symptoms of anxiety. Unlike the benzodiazepines, which have a direct anxiolytic effect, its full clinical effectiveness may require 1 to 2 weeks to manifest, and the somatization symptoms are even improved more slowly.
Buspirone is only used to treat anxiety disorders in patients over 18 years of age and used for the short-term relief of symptoms of anxiety. The safety and efficacy of this drug in children and adolescents remains unclear.

Pharmacokinetics

Buspirone is absorbed fast and completely when taken by mouth and the time to peak plasma levels following ingestion is within 0.5 to 1 hour. There is a liver first-pass metabolism, and t1/2 is 1 to 14 hours, and the plasma protein binding rate is 95%. Most of them are metabolized in the liver. Major metabolites of buspirone include 5-hydroxy buspirone and 1-(2-pyrimidinyl)-piperazine, which still have some biological activity. After oral administration, about 60% is excreted in the kidneys and 40% is excreted in the feces. The first-pass metabolism is reduced for patients with cirrhosis, so the peak plasma levels areis increased, and the drug elimination rate is significantly reduced. The elimination rate is slightly reduced for patients with renal dysfunction. No special pharmacokinetics changes have been found in elderly patients.

Drug combination

Azapirone anxiolytic drugs are a new generation of anxiolytic drug introduced in recent years. It is one of the commonly used drugs in the treatment of neurological disorders, represented by buspirone and tandospirone, as they act on 5-HT1A receptor, also known as 5-HT, a anxiolytic drug. These drugs have an anxiolytic activity but no sedative/hypnotic and anticonvulsant effects. Buspirone is less effective for generalized anxiety disorder (GAD) than benzodiazepine BDZ, but it is effective for less severe GAD and may be effective in 60% to 80% of patients with previous BDZ ineffectiveness. It is not as effective as BDZ and some antidepressants when used in the treatment of severe anxiety with panic attacks. The use of buspirone alone in the treatment of obsessive-compulsive disorder is not effective, but it has been reported that anti-coercive effect has been shown when used in combination with 5-HT antidepressant. It has also been suggested that use BDZ in combination with buspirone may be more effective than either drug alone due to their different mechanism of action. But generally joint use is not suggested.

Side effects

Common: nausea, diarrhea (3%), headache (7%), dizziness (9%), nervousness (4%), agitation (2%) and insomnia. 
Uncommon: blurred vision, distracted attention, cachexia (when dosage greater than 20 mg), dry mouth, muscle pain, muscle spasm, myotonia, tinnitus, stomach upset, sleep disorders, nightmares, multiple dreams, fatigue and weakness. Rare: chest pain, mental disorders, depression, tachycardia, muscle weakness, muscle numbness, and weakness in the hands and feet.

Precautions

(1) Buspirone is contraindicated in patients with hypersensitivity to Buspirone, severe liver and kidney dysfunction, acute angle-closure glaucoma, myasthenia gravis, pregnancy, children and young people under the age of 18.

(2) Driving or operating the machine must be avoided during the medication.

(3) Physical dependence is rarely developed.

(4) No clinical experience has been existing for Buspirone use in combination with the following drugs: antihypertensive drugs, antidiabetic drugs, anticoagulants, contraceptives, cardiotonic and so on, so use it with care.