Anxiolytic drugs experiments

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. 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

The efficacy of benzodiazepines in most anxiety disorders has been proved through extensive clinical experience and controlled trials (Faravelli et al. 2003), although it is important to note that they are not effective at treatingpost-traumatic stress disorder or comorbid depression, and there is less evidence to support their use in obsessive-compulsive disorder (OCD). Their anxiolytic effects have an immediate onset and in contrast to many other drugs, they do not cause a worsening of anxiety when therapy is initiated. 

Historically, Saletu (1976) performed a series of EP experiments in health subjects to stud the action of several antipsychotics, antidepressants, anxiolytics and psychostimulants. Similar to Fink and Itil for the pharmaco-EEG, he reported on systematic, drug-type-related changes in EP latencies after somatosensoiy stimulation of his subjects. 

One of the problems associated with benzodiazepine anxiolytics is rebound anxiety and/or insomnia, which may occur between dose intervals or after withdrawal of the drug [83, 84], In three experiments performed with squirrel monkeys, (92) (up to 20 mg/kg p.o.) did not cause any apparent physical or behavioural signs of withdrawal after abrupt discontinuation of treatment or even after attempted precipitation of withdrawal by administration of flumazenil. 

Functional MR was applied mainly to the studies of the auditory, sensory, motor and visual realms of the brain. Experiments on the response of the brain to intestinal sensation and to pain are in progress [70]. It is obvious that human brain mapping should include studies on the effect of drugs stimulating, seductive, anxiolytic etc. It opens a new research field of great importance for pharmacy. 

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