Article: Buspirone

Buspirone
Systematic (IUPAC) name
8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]- 8-azaspiro[4.5]decane-7,9-dione
Identifiers
CAS number	36505-84-7
ATC code	N05BE01
PubChem	2477
DrugBank	APRD00222
Chemical data
Formula	C21H31N5O2
Mol. weight	385.503 g/mol
Pharmacokinetic data
Bioavailability	low and variable (approx. 5%), due to high first pass metabolism
Metabolism	mainly hepatic, active metabolite 1-Pyrimidylpiperazin (1-PP)
Half life	2-3h
Excretion	urine (29-63%) and feces (18-38%) in the form of metabolites
Therapeutic considerations
Pregnancy cat.	B, only use when clearly needed
Legal status	Rx-only, not a controlled substance
Routes	oral

Buspirone (brand-names Ansial®, Ansiced®, Anxiron®, Axoren®, Bespar®, BuSpar®, Buspimen®, Buspinol®, Buspisal®, Narol®) is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam.

It shows no potential for addiction compared to other drugs commonly prescribed for anxiety, especially benzodiazepine medications. The development of tolerance has not been noticed. Cross-tolerance to benzodiazepines, barbiturates and alcohol does not exist. Furthermore, it is non-sedating.

It is thought to act by interfering with the function of the neurotransmitter serotonin in the brain, particularly by serving as a 5-HT1A receptor partial agonist. Additionally, it acts as a mixed agonist/antagonist on postsynaptic dopamine receptors. GABA-mediated effects are lacking. Buspirone may also have indirect effects on other neurotransmitters in the brain.

The action of a single dose is much longer than the short halflife of 2-3 hours indicates. The bioavailability of Buspirone is very low and variable due to extensive first pass metabolism. The drug is quickly resorbed. Taking the drug together with food may increase the bioavailabilty. The drug is highly (95%) plasma-bound. The active metabolite 1-PP is also a 5-HT1A partial agonist with anxiolytic properties, but weaker so than the mother-drug.

It is also useful as an augmenting agent, for the treatment of depression, when added to SSRIs (selective serotonin reuptake inhibitors).

The main disadvantage is that 1 to 3 weeks elapse before the anxiolytic activity becomes evident. Often patients have to be initially cotreated with a benzodiazepine for immediate anxiolysis. Generally, Buspirone works less well than benzodiazepines. It is particularly difficult to treat patients pretreated with benzodiazepines knowing the immediate effects of these tranquilizers.

Bristol-Myers Squibb gained FDA approval for Buspirone in 1986. The drug went generic in 2001.

Indications

• Generalized anxiety disorder of mild to moderate intensity (N.B. Buspirone is not considered effective against other types of anxiety disorders with or without agoraphobia and social phobia.)
• Augmention of SSRI-Treatment against Depression

Contraindications

• Myasthenia gravis
• Acute closed angle glaucoma
• Severely compromised liver- and renal-function
• Concomittant treatment with a MAO-Inhibitor (severe hypertensive crises have been seen)
• Caution : Preexisting heart conditions (e.g. myocardial infarction)

Side-effects

Rarely, side-effects have a dangerous nature or intensity. Some tend to disappear with continued therapy, or are less frequent if the initial dose is low and increased gradually (vertigo, agitation, insomnia).

• Most frequent: vertigo, headaches, nervousness, agitation, light-headedness, nausea;
• Often (>1%) : drowsiness, insomnia, concentration disorders, confusion, depression, agitation, intestinal disorders, paresthesia, coordination disorders, tremors, disturbed vision, tinnitus, fatigue, weakness, Angina pectoris, sore throat, tachycardias, palpitations, dry mouth, pain in muscles and joints;
• Seldomly: allergic reactions, subdermal bleeding, extrapyramidal symptoms, hallucinations, psychosis, ataxia, epileptic seizures, syncope, tunnel vision, urine retention, alopecia, pruritus.

The dyscognitive side-effects of benzodiazepines are lacking completely.

Other side-effects have been seen, but are not more frequent than those encountered with placebo. An unusual side effect reported by patients has been an enhanced sense of smell.

Drug abuse and dependence

Buspirone has no known potential for abuse, psychological and physical dependence.

Interactions

• Haloperidol : increased plasma-levels of Haloperidol
• Rifampizin : decreased plasma-levels of Buspirone
• MAO-Inhibitors : severe hypertensive crises are possible.
• Alcohol : The sedative properties of alcohol are not increased.
• Grapefruit, Grapefruit juice, Grapefruit extract : drastically increased plasma-levels of Buspirone ^{[1][2][3][4]...}

Dosage

Initially, 10-15mg in 2-3 single doses per day. The dose may be increased to a maximum of 60mg daily (3 times 20mg, a single dose should not exceed 20mg).

Duration of treatment

The duration of treatment is not limited, but the prescribing physician should reassess in regular intervals, if continued treatment is still necessary.

Other remarks

Buspirone should not be used as a substitute for benzodiazepines, barbiturates or alcohol before withdrawing these agents properly. No residual signs of withdrawal should exist when Buspirone is started. Buspirone is not able to alleviate any withdrawal symptoms caused by these drugs.