Anxiolytic drugs indications

Food intake is considered a reliable indicator for the anxiolytic properties of drugs. Rodents usually are reluctant to eat unknown food (Boissier et al. 1976 Soubrie et al. 1975). When both famiUar and unknown food are presented, rodents will typically show a longer latency to the first intake of imknown food compared to the intake of famihar food. Anxiolytic drugs not only reverse this food intake inhibition (Fletcher and Davies 1990 Hodges et al. 1981) but also result in an increased consiunption of food (Britton and Britton 1981). 

Referred to as a conditioned fear paradigm, the fear potentiated startle response was first described by Brown et al. (1951). In the original test, an acoustic stimulus is presented in the presence of a conditioned stimulus that has previously been paired with an aversive, unconditioned stimulus. The amplitude of the acoustic startle response is thought to indicate the degree of conditioned anxiety, which can be reduced by anxiolytic drugs (Davis et al. 1993 Hijzen et al. 1995). 

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]. 

Levorphanol (Levo-Dromoran) is an L-isomer morphi-nan derivative of morphine that is five to seven times more potent than morphine. It produces all of the side effects associated with morphine but less nausea. It is indicated for moderate to severe pain as a preoperative anxiolytic. It is often used in combination with thiopental to reduce the latter drug s anesthetic dose and to decrease postoperative recovery time. The o-isomer of levorphanol, dextrorphan, does not possess opioid analgesic activity but is a useful antitussive. 

The benzodiazepines constitute the most commonly used group of anxiolytics and sedative-hypnotics. Since the first member of this group, chlordiazepoxide, was introduced, many congeners have been marketed. Most of these drugs possess anxiolytic, sedative-hypnotic, and anticonvulsant properties. Thus, the clinical indications for specific benzodiazepines are not absolute, and their uses overlaps considerably. 

S-HTjc, and 5-HTj receptors may be especially involved in the serotonin system s response in anxiety. Most interest has focused around 5-HTj, drugs (buspirone, ipsapirone, gepirone, tandospirone, flesinoxan, and others]. Some preclinical data indicate that antagonists at S-HTj, S-HTj, and 5-HT3 receptors may also exert anxiolytic activity, but so far these findings have not been consistently confirmed in clinical trials. 

Problems of optimal dosage and duration of drug treatment for mental disorders have also been addressed in numerous controlled studies and are presented separately below for antipsychotics, antidepressants, mood stabilizers, anxiolytics and psychostimulants. This division again makes sense because the disorders treated and the therapeutic approaches used differ in significant aspects and the empirical studies carried out in the individual indications show major qualitative and quantitative differences. 

Chapter 1 introduced the benzodiazepine anxiolytics as drugs with a very broad but not always clearly delimited range of indications in almost all branches of medicine. In the present connection we are concentrating on the most common uses of these drugs in psychiatry, i.e. on anxiety disorders. According to DSM-IV (APA 1994), these are ... 

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