Benzodiazepines central nervous system disorders

Quinazolino-1,4-benzodiazepines are useful in the treatment of some central nervous system disorders [79GEP(0)2758875] and showed chole-cystokinin antagonist activity (85USP4554272, 85USP4559338). 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Nearly all central nervous system depressants have some capacity to suppress seizures by virtue of their depressant activity on the brain and spinal cord. Clonazepam and diazepam are two benzodiazepines that depress epileptiform activity and are used in the treatment of epilepsy and seizure disorders (see Chapter 32). 

During the early twentieth century the barbiturates were used in children and adolescents for their sedative and hypnotic effects however, their safety profile and propensity to cause physical dependence led scientists in search of safer anxiolytics. The development of animal models of behavioral disorders facilitated the formulation of drugs with more specific central nervous system (CNS) effects. In 1959, chlordiazepoxide (Librium) was the first benzodiazepine (BZ) to receive a patent. It entered the market in 1960, followed by diazepam (Valium) in 1963. Today, over 35 BZs have been formulated and over 10 are available in the United States (Ballenger, 1995 Hobbs et ah, 1996). 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

The l-(hetero)arylvinyl-5//-2,3-benzodiazepines, useful for the treatment of central nervous system (CNS) disorders, are prepared by the reaction of 2-benzopyrylium perchlorates with hydrazine hydrate <2001EPP0726257B1>. 

Dni used for the management of convulsive disorders are called anticonvulsants. Most anticonvulsants have specific uses, tliat is, tliey are of value only in the treatment of certain types of seizure disorders. There are five types of dru used as anticonvulsants barbiturates, benzodiazepines, hydantoins, oxazolidinediones, and tlie succinimides. In addition, several miscellaneous dni are used as anticonvulsants. All possess the ability to depress abnonnal neural discharges in tlie central nervous system (CNS), resulting in an inhibition of seizure activity. Dni tliat control generalized tonic-clonic seizures are not effective for absence (petit mal) seizures. If botli conditions are present, combined drug tlierapy is required. 

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