Histamine Hi Antagonists Antihistaminic Agents

In many of the first-generation, or classical, antihistamines. the terminal nitrogen atom is a simple dinicthylainiiw moiety. The amine may also be part of a heterocyclic stnic-ture. however, as illustrated by (he piperazines, some pin-pylamincs (pyrrolidines and piperidines), some phenMhia-zines. the dibenzocycloheptenes. and (he sccond-generatwn 

A number of the antihistamines, particularly the phenothi-azines and aminoalkyl ethers, have antiemetic actions and thus may be u.seful in the treatment of nausea, vomiting, and motion sickness. Also, those agents that produce pronounced. sedation have application as nonpiescription sleeping aids. - Several of the phenothiazines have limited u.se in Parkinson-like syndromes as a result of their ability to block central muscarinic receptors. -And. a number of antihistamines, including promethazine, pyrilamine. tri-pelennamine and diphenhydramine, display local anesthetic activity that may be therapeutically useful.  

The Hi antagonists display a variety of. significant drug interactions when coadministered with other therapeutic agents. For example. MAO inhibitors prolong and intensify the anticholinergic actions of the antihistamines. -  

the sedative cffecLs of these agents may potentiate the deprcssutit activity of barbiturates, alcohol, narcotic analgc-.sics. and other depressants. Recently, it was discovered that several of the second-generation antihistamines may produce life-threatening arrhythmias when coadminkstcred with drugs that inhibit their metabolism. -These interactions arc di.scussed in more detail in the. sections below. 

The simple diphenyl derivative diphenhydramine was the first clinically useful member of the cthanolamine series and serves us the prototype. Other therapeutically useful derivatives- of diphenhydramine have been obtained by para substitution of methyl (methyidiphcnhydraminc). methoxy (me-drylamine). chloro (chlorodiphcnhydraminc). or bromo (bromixliphenhydraminc) on one of the phenyl rings. These derivatives reportedly have better therapeutic profiles than diphenhydramine becuu.se of reduced adverse effects. -  

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