Antihistamine-like activity

Fixed dose combination or centrally acting antitussive with antihistaminics having atropine like activity in expectorants. 

Antihistamines bind to the same active site of the enzyme that binds histamine in the cell, but they evoke a different response. An antihistamine like bFompheniramine, for example, inhibits vasodilation, so it is used to treat the symptoms of the common cold and allergies. Cimetidine (trade name Tagamet) is a histamine mimic that blocks the secretion of hydrochloric acid in the stomach, so it is used to treat individutils with ulcers. 

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

B. Although scopolamine effectively combats motion sickness, it is an antimuscarinic agent, not an antihistamine. Dimenhydrinate is an antihistamine with signihcant antimuscarinic properties that are likely to contribute to its anti-motion sickness activity. Chlorpheniramine, fexofenadine, and tripelennamine are antihistamines without signihcant efficacy in the treatment of motion sickness. 

The butyrophenones and diphenylbutylpiperidines differ from the phenothia-zines and thioxanthines in that they are not tricyclic structures. The first butyrophenone to be developed was haloperidol, and this is the most widely used, potent neuroleptic. Unlike many of the phenothiazines, these neuroleptics largely lack antihistaminic, anticholinergic and adrenolytic activity they are also non-sedative in therapeutic doses. Their potent antidopaminergic activity renders them likely to cause extrapyramidal side effects. Of the various butyrophenones shown in Figure 11.10, benperidol has been selectively used to suppress asocial sexual behaviour. 

Benzatropine and ethylbenzatropine are particularly likely to interact additively with other drugs with both anticholinergic and antihistaminic activity, such as neuroleptic drugs complications such as hyperpyrexia, coma, and toxic psychosis have been reported several times when such combinations were used (626-628). 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Like other antihistamines that rely on activation by metabolism, the systemic availability of ebastine can be affected by food. In a double-blind, placebo-controlled, parallel-group study, 215 patients with seasonal allergic rhinitis took ebastine with solid food (immediately after breakfast), while 218 took it 1-2 hours after breakfast (7). Food taken at the time of dosing did not alter the therapeutic or adverse effects of ebastine for 2 weeks in seasonal allergic rhinitis. Although carebastine steady-state concentrations were 15% higher when ebastine was taken with food this was not considered clinically important. 

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. ... 

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