It is an orally active anxiolytic drug that is pharmacologically and structurally different from other anxiolytics such as benzodiazepines and barbiturates. Buspirone also differs from other anxiolytics in that it does not have muscle relaxant or anticonvulsant activity, nor does it cause dependence or sedation. In this way, buspirone has the great advantage of not deteriorating the state of wakefulness and attention. Buspirone is not used for the immediate relief of anxiety.since its effects take two weeks to become apparent. Immunosuppressive properties of buspirone have recently been discovered and clinical studies are underway to determine its efficacy in atopic dermatitis.
Ansial®; Ansiced®; Anxiron®; Axoren®; Bespar®; Buspar®; Buspimen®; Buspinol®; Buspisal®; Narol®
Mechanism of action
In general, buspirone suppresses serotonergic activity while increasing adrenergic and dopaminergic activity of cells . Buspirone does not inhibit monoamine oxidase, nor does it have significant activity on benzodiazepine or GABAergic receptors. However, buspirin shows a certain inhibitory effect on GABA-mediated neuronal pathways.
In vitro, buspirone shows a higher affinity for type 1A serotonin receptors, a moderate affinity for type 2 dopamine receptors, and a weak affinity for type 2 serotonin receptors. Serotonin type 1A receptors are found in large numbers. in the dorsal raphe and in the hippocampus. Buspirone binds to 1A receptors at these sites, on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus. Animal studies show that buspirone inhibits the excitation rate of 5-HT-containing neurons in the dorsal raphe.
The predominant action of buspirone is partial agonism or mixed antagonism / agonism at 5-HT1A receptors. Buspirone also binds to dopamine type 2 (DA2) receptors, showing the effects of a dopamine antagonist and agonist. Buspirone blocks presynaptic receptors, while its postsynaptic effects are conflicting. Buspirone differs from gepirone, a similarly structured product under investigation that does not bind to dopamine receptors. Buspirone increases the excitability of neurons in the locus ceruleus, an area of the brain where norepinephrine is found in high concentrations, unlike benzodiazepines that depress excitability in this area. This difference would explain why benzodiazepines cause drowsiness while buspirone does not. The net result of all these effects is the inhibition of second messenger synthesis and release. However, as anxiety is believed to be caused by various nervous processes, this inhibition of serotonin synthesis and release does not complexly explain the anxiolytic effect of buspirone. Clinically, buspirone relieves symptoms associated with a generalized anxiety disorder such as motor tension (restlessness,
The immunosuppressive effects of buspirone are not related to its anxiolytic action. Buspirone has no muscle relaxant, anticonvulsant activity and does not produce dependency when administered chronically.
After oral administration, buspirone is almost completely absorbed although only 4% reaches the systemic circulation due to significant first-pass metabolism. The onset of anxiolytic effects are observed at 3-6 weeks. The distribution of buspirone in the body has not been fully elucidated. In vitro studies show that buspirone is 86% bound to plasma proteins. Buspirone and its metabolites are excreted in milk. The metabolism of the drug takes place mainly in the liver where it is oxidized and its conjugated metabolites. The main metabolite of buspirone does not have anxiolytic activity. Most of the drug and its metabolites are eliminated via the kidneys and, to a lesser extent, via the bile. In healthy volunteers, the elimination half-life of buspirone is 2-4 hours and longer in patients are renal or hepatic insufficiency. After multiple doses to patients with renal or hepatic impairment, the steady-state AUC of 13 and 4 times higher than in normal subjects.
Contraindications and Warnings
Buspirone is absolutely contraindicated in patients with known hypersensitivity to the drug.
Buspirone does not show cross tolerance with benzodiazepines and other common sedatives or hypnotics. Buspirone does not block the withdrawal syndrome often seen when benzodiazepine treatment is discontinued. Therefore, before starting treatment with buspirone, the doses of benzodiazepine or other drugs active on the CNS should be reduced. In the case of benzodiazepines, the withdrawal phases of these can be superimposed with that of the start of buspirone, taking into account that the anxiolytic effects of this take a minimum of two weeks to manifest.
Co-administration of buspirone and monoamine oxidase inhibitors (MAOIs) is not recommended.
Administration of buspirone should be done with caution in subjects with renal impairment because the drug or its metabolites can accumulate. Precautions should also be taken in patients with hepatic impairment as buspirone is extensively metabolized in the liver. The administration of this drug is not recommended in cases of severe liver failure.
Although clinical studies indicate that buspirone causes less sedation than other anxiolytics and that it does not cause functional impairment, its effects on a particular individual are not predictable. Therefore, patients should be warned if they operate machinery or if they drive. Although no interference of buspirone with alcohol has been observed in clinical studies, it seems prudent to refrain from alcoholic beverages. Because buspirone binds to dopamine receptors in the central nervous system, its potential to cause acute and chronic changes in dopamine-dependent neurological function (e.g., dystonia, suedoparkisonism, akathisia and tardive dyskinesia). Results from clinical trials have not identified any significant neuroleptic activity; however, a syndrome of nervousness that appears shortly after starting treatment has been reported in a small number of patients treated with buspirone.
Buspirone is classified in pregnancy risk category B. No changes in fertility or fetal damage have been observed in reproduction studies carried out in rats and rabbits at doses up to 30 times higher than those of humans. However, there are no controlled clinical studies in man, and since animal studies are not always predictive of what may occur in humans, the use of buspirone in pregnancy is not recommended or unless there is a clear need. The extent to which buspirone is excreted in human milk is not known, therefore the administration of this drug during lactation is not recommended.
The simultaneous use of buspirone with monoamine oxidase inhibitors (MAOIs) can increase blood pressure, therefore the use of this combination is not recommended. If the patient is treated with MAOIs, a washout period of 14 days is recommended before starting treatment with buspirone.
Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect is unknown. In vitro studies have shown that aspirin can increase plasma concentrations of buspirone by 23% and that flurazepam decreases them by 20%, but no in vivo studies on this interaction have been performed. Other in vivo studies have shown that buspirone does not displace proteins from other drugs such as phenytoin, warfarin or propranolol.
The combination of buspirone with other sedatives or central nervous system depressants may cause additive effects. CNS depressants include anxiolytics, sedatives, and hypnotics; benzodiazepines, barbiturates, butorphanol, nalbuphine, pentazocine, tricyclic antidepressants, antipsychotics, opioid agonists, tramadol, entacapone and some gaping H1 (eg, brompheniramine , carbinoxamine , chlorpheniramine , clemastine , dimenhydrinate , diphenhydramine , doxylamine , methdilazine , promethazine ,trimeprazine ).
Concomitant use of buspirone and haloperidol results in increased plasma concentrations of haloperidol, possibly due to competition between oxidative dealkylation. The clinical significance of this interaction is unknown.
The joint use of buspirone and fluoxetine has produced variable results. From a pharmacological point of view ,. These two drugs have opposite actions: buspirone reduces the synthesis and release of serotonin through serotonergic receptors while fluoxetine enhances serotonin by blocking its reuptake. The addition of fluoxetine to a regimen consisting of buspirone and trazadone resulted in increased anxiety in a subject treated for his generalized anxiety and panic disorder. However, in patients with obsessive compulsive disorders, the combination of buspirone and fluoxetine has been reported to produce better results.
Coadministration of buspirone with verapamil or diltiazem increases buspirone plasma concentrations substantially (approximately 3-fold).
Due to the potential risk of a serotonin syndrome, precautions should be taken when administering drugs that act selectively on serotonin reuptake (such as venlafaxine, for example) and other drugs that may have serotonin effects on the CNS.
Linezolid has reversible, non-selective monoamine oxidase inhibitor properties. It is not recommended in simultaneous use of linezolid and buspirone. A 10-day washout period of linezolid should be performed before initiating buspirone treatment.
Although food improves the gastrointestinal absorption of buspirone slightly, from a practical point of view it makes no difference whether the drug is taken with or without food.
Grapefruit juice has been shown to slightly increase buspirone plasma concentrations, probably due to its inhibitory effect on CYP3A4 isoenzymes in the digestive tract. They may therefore increase drowsiness and other subjective side effects of buspirone, so patients should be advised not to consume this juice during buspirone treatment.
The most common adverse reactions observed during buspirone treatment are effects on the central nervous system such as dizziness (which occurs in 12% of cases), drowsiness (in 10% of cases, headaches ( 6%) and nausea / vomiting (6-8%) Some patients show a syndrome of restlessness with nervousness and excitement (between 2 and 5%).
Other less frequent side effects that have been observed in patients treated with buspirone are: hostility, anger, confusion. blurred vision, myalgia, swelling, paresthesia, tremors, weakness, and sweating.
In clinical studies in more than 3,500 patients, other side effects were observed in less than 1% of cases including chest pain, nightmares, tinnitus, dry mouth and nasal congestion, some (very rare) allergic reactions, angioedema, ataxia, dyskinesia , ecchymosis, extrapyramidal syndromes, urinary retention and dystonic reactions. However, it is very clear that there is a causal relationship between these effects and buspirone treatment.
- BUSPAR, comp 10 mg. BRISTROL-MYERS
- EFFIPLEN, comp 5 and 10 mg. EFFIK
- NAROL, comp 5 and 10 mg. ALMIRALL-PRODESFARMA