Peripheral selectivity

Two different types of P-adrenoceptors have been characterized and categorized as P - and P2-subtypes. The P -receptors are associated primarily with the cardiac muscle, whereas the P2-subtype is located peripherally. Selective P -blockers include practolol (121) and (122), atenolol (123) and (124), and betaxolol (125) and (126). 

Although leukotriene antagonists represent a new therapeutic alternative, published studies to date have shown them to be no more effective than peripherally selective antihistamines and less effective than intranasal corticosteroids. However, combined use with antihistamines is more effective than antihistamine treatment alone. 

Rocha B, von Boehmer H Peripheral selection of the T cell repertoire. Science 1991 251 1225-1228. 

Opioid antagonists (Table 7.4), predominantly naloxone, are used clinically to reverse the effects of opiates in overdose or postoperative sedation. Naltrexone, which has oral bioavailability, is used for the treatment of narcotic addiction and alcohol dependence. As discussed below (Section 2.2.2.1), peripherally selective antagonists are being evaluated for treatment of constipation and other gastrointestinal side effects associated with opioid agonist use. 

Botros S, Lipkowski AW, Larson DL, Stark AP, Takemori AE, Portoghese PS (1989) Opioid agonist and antagonist activities of peripherally selective derivatives of naltrexamine and oxymorphamine. J Med Chem 32 2068-2071... 

Piperidine class, peripherally selective Desloratadine Low to none Low to none... 

While many clinicians strongly prefer a peripherally selective agent as the first antihistamine choice, economic considerations still result in the first-line choice of the less expensive and more sedating products by some prescription plans and clinicians. 

Numerous products combine an antihistamine with a decongestant. The combination is rational because of the different mechanisms of action. Both nonselective and peripherally selective antihistamines are available in such combinations. As mentioned previously, patients should read labels to avoid therapeutic duplication. 

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