The reaction mechanisms, selectivity and specificity of action of 2-halogenoethylamines-An analysis

The design of monofunctional 2-halogenoethylamines as irreversible antagonists to the excitatory responses produced by noradrenaline has met with considerable success and extremely active and highly specific compounds are now known. The design of difunctional analogues (nitrogen mustards) as irreversible anti-tumor agents has not enjoyed the same success. It is the purpose of this paper to analyse this situation in terms of previous work and to indicate features which may be pertinent to the design of more effective anti-adrenaline and anti-tumor agents. Particularly, the activities of both mono- and di-functional 2-halogenoethylamines are discussed in terms of their specificity (antagonism to a specific biochemical process) and selectivity (localization at a particular cellular level) of action. The biological actions of 2-halogenoethylamines are discussed in terms of their chemical reactivity which is apparently a necessary, but not a sufficient, prerequisite for both adrenergic blocking and anti-tumor activities. However, a limited correlation between chemical reactivity and biological activity may sometimes be apparent. The importance of factors influencing both specificity and selectivity of action are critically discussed, and it is suggested that specificity of action only is concerned with adrenergic blocking action, but that both selectivity and specificity of action are of importance in the design of effective anti-tumor agents.