Anxiety Anxiolytics

Water-soluble vitamin (part of the vitamin B group). It has demonstrated anti-inflammatory actions. Animal studies show that nicotinamide has anti-anxiety (anxiolytic) properties. 

Anxiolytics are compounds that act primarily to refleve the symptoms of anxiety although such agents can also be used as anticonvulsants, sedatives, hypnotics, and anesthetic agents (see Anesthetics). The principal class of anxiolytics, the BZs, shows dependence HabiUty (5) whereas newer agents such as buspkone [36505-84-7] and ritanserine [8705-43-2] produce antianxiety effects via central serotoninergic systems (6). 

Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

Glassification of Substance-Related Disorders. The DSM-IV classification system (1) divides substance-related disorders into two categories (/) substance use disorders, ie, abuse and dependence and (2) substance-induced disorders, intoxication, withdrawal, delirium, persisting dementia, persisting amnestic disorder, psychotic disorder, mood disorder, anxiety disorder, sexual dysfunction, and sleep disorder. The different classes of substances addressed herein are alcohol, amphetamines, caffeine, caimabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics, polysubstance, and others. On the basis of their significant socioeconomic impact, alcohol, nicotine, cocaine, and opioids have been selected for discussion herein. 

Anxiolytic. A drug that decreases the mental symptoms and somatic signs of anxiety. 

Minor tranquilizer. A drug useful in the control of anxiety. Also referred to as anxiolytic. 

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. 

Benzodiazepines are amongst the most frequently prescribed drugs they have well-established uses in the treatment of anxiety disorders (anxiolytics) and insomnia, preanaesthetic sedation, suppression of seizures, and muscle relaxation. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Out-patient treatment is substantially cheaper than in-patient management and is generally as effective (Lowman, 1991). A French study on patients with generalized anxiety disorder estimated costs per patient over 3 months to he US 423 for hospitalization, 335 for out-patient services and 43 for medications (Souetre et al, 1994). Comorbid conditions (mostly alcoholism and depression) doubled these direct health-care costs. Over three-quarters of all patients were taking anxiolytic medication. 

Finally, the peptide can induce anxiety and panic in normal and anxious volunteers. Some synthetic CCK-B receptor antagonists are chemically similar to the benzodiazepine anxiolytics. Again, the clinical role of CCK manipulation in anxiety remains to be resolved. 

Several neuropeptides are under current investigation for their role in anxiety disorders. Important neuropeptides include neuropeptide Y (NPY), substance P, and cholecystokinin. NPY appears to have a role in reducing the effect of stress hormones and inhibiting activity of the LC. Both mechanisms may contribute to the anxiolytic properties seen experimentally. Substance P may have anxiolytic and antidepressant properties. This may be due in part to its effects on corticotropin-releasing hormone.21... 

Mischoulon, D. (2002). The herbal anxiolytics kava and valerian for anxiety and insomnia. Psychiatric Annals, 32, 55-60. 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

Argyropoulous SV, Sandford JJ and Nutt DJ (2000). The psychobiology of anxiolytic drugs. Part 2 Pharmacological treatments of anxiety. Pharmacology and Therapeutics, 88, 213-227. 

Anxiolytic The most commonly prescribed type of psychotropic drug, used chiefly to treat generalised anxiety disorders. 

Sandler M (1992). Development of anxiolytic and antidepressant drugs A historical perspective. In JM Elliot, DJ Heal and CA Marsden (eds), Experimental Approaches to Anxiety and Depression (pp. 1-8). John Wiley Sons, Chichester, UK. 

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