Benzodiazepines, anxiolytic action side-effects

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Buspirone is an extremely specific drug that could possibly represent a new chemical class of anxiolytics—azaspirones. As an anxiolytic, its activity is equal to that of benzodiazepines however, it is devoid of anticonvulsant and muscle relaxant properties, which are characteristic of benzodiazepines. It does not cause dependence or addiction. The mechanism of its action is not conclusively known. It does not act on the GABA receptors, which occurs in benzodiazepine use however, it has a high affinity for seratonin (5-HT) receptors and a moderate affinity for dopamine (D2) receptors. Buspirone is effective as an anxiolytic. A few side effects of buspirone include dizziness, drowsiness, headaches, nervousness, fatigue, and weakness. This drug is intended for treatment of conditions of anxiety in which stress, muscle pain, rapid heart rate, dizziness, fear, etc. are observed in other words, conditions of anxiety not associated with somewhat common, usual, and everyday stress. Synonyms for buspirone are anizal, axoren, buspar, buspimen, buspinol, narol, travin, and others. 

In summary, buspirone is an effective generalized anxiety treatment that differs from conventional antianxiety drugs in speed of symptom reduction and types of symptoms affected. Although buspirone might seem to be the drug of choice for treatment of chronic anxiety, it has not displaced the use of benzodiazepines in the treatment of anxiety, perhaps because of its side-effect profile [dizziness, sedation, nausea], slow onset of action, and the opinion of some clinicians that its anxiolytic efficacy is less robust than that of benzodiazepines. Buspirone is accepted as an anxiolytic treatment much more widely in the United States than in most other countries [Kunovac and Stahl 1995]. 

How is a specific objective within the R D portfolio, e.g. the search for anxiolytic drugs with a fast onset of action (like benzodiazepines) but lacking cognitive side effects and addictive potential (unlike benzodiazepines), to be partitioned and sequenced so that individual groups within R D, with their different approaches and methods, can be integrated sensibly into the project ... 

Actions at benzodiazepine receptors are thought to underlie virtually all the pharmacological actions of the benzodiazepines, those that are desirable as well as those that are undesirable. This includes the desirable therapeutic actions of benzodiazepines as anxiolytics and sedative-hypnotics, as well as anticonvulsants and muscle relaxants. It also includes their undesirable side effects as amnestic agents and as agents that cause adaptations at the benzodiazepine receptor with chronic administration, which are thought to underlie the production of dependence and withdrawal from these agents (see Chapter 13). 

The pharmacology of benzodiazepine derivatives differs significantly from that of the neuroleptics, in that the benzodiazepines have no psychoplegic (antipsychotic) activity and cause no extrapyramidal, autonomic, or endocrine side effects. In addition, unlike the neuroleptics, which lower the seizure threshold, these substances are anticonvulsants. In addition, they are anxiolytics, muscle relaxants, and mild sedatives. Although the benzodiazepine derivatives do not produce pronounced autonomic or CV side effects, they can reduce or block the emotionally induced changes in cardiovascular functions, probably through actions on the limbic system. 

The triazolopyridazine CL 218,872 is another research tool used to probe BZR heterogeneity, because it is known to have selective high affinity at BZR subtypes containing the a1 subunit, hypothesized to mediate anxioselective actions (84,122). CL 218,872 has lower efficacy than benzodiazepines in potentiating GABA-gated chloride currents, but it produces anxiolytic effects in animal models at substantially lower doses than those required to produce untoward side effects (e.g., sedation, ataxia, and muscle relaxation) (78,122). 

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