Benzodiazepines, specific agents alprazolam

Benzodiazepines are highly effective anxiolytics and sedatives. They also have muscle relaxant, amnestic, and anticonvulsant properties. Benzodiazepines effectively treat both acute and chronic generalized anxiety and panic disorder. The high-potency benzodiazepines alprazolam and clonazepam have received more attention as antipanic agents, but double-blind studies also have confirmed the efficacy of diazepam and lorazepam in the treatment of panic disorder. Although only a few benzodiazepines are specifically approved by the... 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system (CNS). Alprazolam like other benzodiazepines exerts its anxiolytic action by potentiating GABA activity. GABA is a neurotransmitter which inhibits the CNS activity. Alprazolam acts preferentially in midbrain, ascending reticular formation (which maintains wakefulness) and on limbic system (thought and mental functions). 

Alprazolam, 269, a popular sedative/hypnotic agent and benzodiazepine receptor agonist, has been labelled257 with 11C in metabolically stable position in reaction of the amidrazone, 7-chloro-5-phenyl-3//-l,4-benzodiazepine-2-yl hydrazone, 270, with 1-[ Cjacetyl chloride followed by pyrolysis of the resulting 1-acetylhydrazone 271. Compound 269 has been obtained in 43-65% yield during 40-55 min at specific activity 0.93-2.18 Ci /miol-1, and used for metabolism and tissue distribution studies257 (equation 107). 

Miscellaneous Agents. Low-dose benzodiazepines, such as 0.25 mg alprazolam three times a day administered before meals, may help reduce anxiety associated with refeeding, although long-term use is not warranted for many patients because of the risk of dependence. One double-blind trial with ondansetron has shown benefit, but the data remain too limited to recommend a specific role for the agent. ... 

Benzodiazepines (alprazolam, diazepam, lonazepam, and lorazepam) reduce fear avoidance, but have little effect on autonomic symptoms. The use of these agents in specific phobia is usually aimed at helping patients to engage in an exposure program and in the case of a specific phobic condition. 

---