Anxiolytics dependence

Sedative/Hypnotic/Anxiolytic Abuse, Sedative/Hypnotic/Anxiolytic Dependence Polysubstance Dependence... 

The biology of the monoamines is described in detail elsewhere. In simple terms, they facilitate transmission in neural pathways that originate in nuclei of the brainstem and have descending projections to the autonomic nervous system and widespread ascending projections to sites in the limbic system and cortex. These pathways modulate many aspects of behavioural function as well as anxiety responses. Of the three monoamines, the role of serotonin in anxiety is best understood, but the picture is complex as increased serotonergic activity may be anxiogenic or anxiolytic depending on the site of action (Bell and Nutt 1998). 

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). 

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. 

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). 

Golombek, D. A, Martini, M. 8r Cardinali, D. P. (1993). Melatonin as an anxiolytic in rats time-dependence and interaction with the central gabaergic system. Eur. J. Pharmacol. 237, 231-6. 

Valerian extracts show sedative and anxiolytic effects. Whereas passionflower and chamomile have relatively specific anxiolytic effects, valerian shows more general sedative effects, but all effects occur in a dose-dependent manner (Della Logia et al. 1981 Leuschner et al. 1993). The sedative effects of valerian extract are moderate when compared to diazepam and the neuroleptic chlorpromazine (Leuschner et al. 1993). However, valepotriates reverse the anxiogenic effects of diazepam withdrawal in rats in the elevated plus maze. This effect is dose dependent, effective at 12 mg/kg but not 6 mg/kg. Interestingly, the fragrant valerian compound bornyl acetate has sedative effects in mice, but only when inhaled (Buchbauer et al. 1992). 

Two studies have been done to date that address ginger s anxiolytic effects in an animal model (Hassenohrl et al. 1996, 1998). Unfortunately, both of these employ a combined treatment of ginger and Ginkgo biloba so they do not allow for differentiation of effects. The combination had diazepamlike effects in an animal model of anxiety (elevated-plus maze) (Hassenohrl et al. 1996). These effects were dose dependent and tripha-... 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

In addition to the benzodiazepine receptor agonists which, depending on the dose administered, have anxiolytic, anticonvulsant, sedative and amnestic properties, benzodiazepines have also been developed which block the action of agonists on this receptor. Such antagonists may be exemplified by... 

The relative contribution of the active metabolites of the benzodiazepines to the overall therapeutic effect of the parent compound will depend on the concentration of the metabolite formed, its agonist potency at central benzodiazepine receptors and its lipophilicity. For example, after the chronic administration of diazepam, desmethyldiazepam accumulates in the brain. As this metabolite has potency at the benzodiazepine receptors equal to diazepam, the metabolite probably plays an important part in the overall action of diazepam. In the case of clobazam, however, even though the active metabolite desmethylclobazam is present in higher concentrations than the parent compound after chronic administration, it has a lower potency than clobazam and therefore is of less importance than the parent compound with regard to the anxiolytic effect. 

In switching drugs, the half-life of elimination that is being stopped should be considered if drug interactions are to be avoided. The time taken for the withdrawal of a drug depends on the duration of treatment sedatives, antiepileptics and anxiolytics may take several weeks to withdraw. 

Depending on their blood levels, both benzodiazepines and barbiturates produce calming and sedative effects, the former group also being anxiolytic. At higher dosage, both groups promote the onset of sleep or induce it (C). 

The development of the benzodiazepine class of drugs for the treatment of a variety of neurological indications has proven to be an outstanting success story in the field of chemotherapy. However, these compounds often produce undesirable side effects when used as anti-anxiety or hypnotic agents. These side effects include sedation, physical dependence, amnesia, muscle relaxation, and ethanol potentiation. The development of a benzodiazepine receptor-based anxiolytic agent devoid of these side effects would constitute a major advance in the field and has been the focus of significant research efforts [284]. 

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. 

Antipsychotics are drugs that have a specific sedative effect, and which improve the attitude and calm the behavior of psychotic patients. They do not cause dependence, and have been proposed for treating psychotic disorders (elimination of psychotic symptomatology— delirium, hallucinations) and schizophrenic patients. Drugs of this group are also frequently referred to as neuroleptics. The term major tranquilizer was used previously to distinguish them from minor tranquilizers/anxiolytics. 

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