Anxiolytic drugs subjective effects

While brain serotonin systems may play a key role in mediating some of the effects of MDMA on analgesia and body temperature as well as in the reported anxiolytic-like and mood-altering subjective effects of the drug, additional neurotransmitter systems may contribute to some of the unique subjective experiences reported for MDMA and other drugs in this class. 

Benzodiazepine abuse is different from other substance abuse disorders (opiates, amphetamines, and nicotine) because benzodiazepines cause much less euphoria and do not activate the classic reward systems that are activated with other substances (mainly the mesolimbic and mesocortical dopaminergic projections). In fact, most people do not find the subjective effects of benzodiazepines pleasant beyond their therapeutic anxiolytic or sleep-inducing effects. Therefore, abuse of benzodiazepines is usually secondary to other substance-abuse disorders, with the benzodiazepine being taken for relief from symptoms induced by the use of another drug. As potential drugs of abuse, short-acting benzodiazepines seem to be preferred among addicts because of the rapidity of their onset of action (aiprazoiam, fiunitrazepam, and iorazepam). 

There are hundreds of published studies on the effects of benzodiazepine anxiolytics and hypnotics on ptr/ermam-e parameters m healthy subjects, and it is generally recognized that these drugs cause a dose-related reduction m most... 

The term minor tranquilizer (which has been replaced by the more precise terms sedative-hypnotic or anxiolytic ) refers to drugs used to treat conditions such as insomnia and anxiety. Because they reduce anxiety and produce pleasantly sedating or tranquilizing effects, these drugs are more subject to abuse than the neuroleptics. 

Little is known about the nervous systems of cestodes and trematodes except that they probably differ from those of nematodes, since milbemycins and avermectins have no effect on them. However, a highly effective anti schistosomal and antitapeworm agent, praziquantel (see Chapter 54 Clinical Pharmacology of the Anthelmintic Drugs), is known to enhance Ca2+ influx and induce muscular contraction in those parasites, though it exerts no action on nematodes or insects. Some benzodiazepine derivatives have activities similar to those of praziquantel these activities are unrelated to the anxiolytic activities in the mammalian central nervous system. The nerves and muscles in schistosomes and tapeworms are thus interesting subjects for future chemotherapeutic studies. 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

Activity at the 5HT-2 receptor is an important feature of many atypical antipsychotic drugs (e.g., risperidone, olanzapine, sertindole), but the body of knowledge on 5HT-2 ligands in anxiety is more limited (173). Nonselective 5HT-2 antagonists, such as ritanserin (112), mianserin (113), and ketanserin (114), have been shown to produce anxiolytic effects in less than half of the preclinical studies conducted (202). The clinical data for ritanserin in human subjects are likewise inconclusive (458, 459). The mixed results obtained with... 

Several clinical studies have shown buspirone (14a) to have anxiolytic efficacy equivalent to that of DZ with significantly less sedation. ° Rats trained to discriminate oxazepam or pentobarbital from vehicle did not generalize to buspirone. At doses above those which are anxiolytically relevant in man, the drug caused a dose-related elevation of plasma prolactin in male subjects, and like the BZ s also increased growth hormone levels. Buspirone elicits a dose-dependent rise in rat striatal dopamine (DA) metabolite levels and may do so by selective antagonism of presynaptic DA autoreceptors with minimal postsynaptic effects. Its catalepsy-reversal effects may occur... 

Even before the identification of central 5-HTg receptors, 5-HTg receptor antagonists have been suggested to possess striking properties. To date, based on animal studies, several reports have shown that these drugs display anxiolytic, antipsychotic [see 3,4, 5,166,167], promnesic [72,169,170], antidepressant [136], antinociceptive [23, 171] and antiemetic [172, 173] properties, generally at low doses and without side-effects [4]. Confirmation of these results in human are necessary before drawing any definitive conclusion since, except for the antiemetic effects, data from clinical trials are few and generally limited to ondansetron. Critical reviews on the subject have recently been published [9, 235-238]. 

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