Antagonist definition

The definitive identifieation of a therapeutie raison d etre for H3 antagonists will happen in the elinie. A handful of H3 ligands are reported to have entered elinieal testing. ABT-834 entered Phase-I trials for the indieation of cognitive disorders in May 2003 but no news has been reported since that time. GT-2331 (11) was approved for Phase-II clinical trials in 1999 but no news has been reported since then [4]. At this point, there are no data available to assess the therapeutic potential in human disease (See Table 5.1). 

In conclusion, H3 ligands offer the attractive vista of multiple applications in various disorders, but the ultimate definition of their therapeutic utility will have to await clinical trial results. Future work will determine whether inverse agonists, neutral antagonists, or protean agonists will constitute the more useful pharmacological intervention. 

Similarly opioid peptides are important in nicotine addiction and may have a role in causing nicotine withdrawal symptoms in some smokers [35]. Opioid antagonists such as naltrexone are licensed treatments for dependence syndromes arising from other addictive drugs and could also be of use in some smokers to aid nicotine withdrawal [59] although there is no definitive evidence overall that they are beneficial [60]. 

Some of the depressant behavioral effects of hallucinogens may involve inhibitory postsynaptic 5-HT receptors. For example, depressant effects of hallucinogens on startle and locomotor activity may result from activation of these receptors, since 5-HT itself has similar effects. Studies on supersensitivity are lacking, however, and, again, the absence of selective antagonists prevents definitive conclusions. 

In addition to epilepsy, neuronal death due to the toxic effects of glutamate has also been implicated in cerebral ischaemia associated with multi-infarct dementia and possibly Alzheimer s disease. With the plethora of selective excitatory amino acid receptor antagonists currently undergoing development, some of which are already in clinical trials, one may expect definite advances in the drug treatment of neurodegenerative disorders in the near future. 

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