Antagonist phenothiazines

Gastrointestinal motility promotors Anti emetics H2 antagonists Phenothiazines 5-ITT inhibitors... 

Gastrointestinal motility promotors Antiemetics H.2 antagonists Phenothiazines 5-HT inhibitors... 

The deliberate or accidental ingestion of natural belladonna alkaloids is a major cause of poisonings. Many histamine Hj-receptor antagonists, phenothiazines, and tricyclic antidepressants also block muscarinic receptors, and in sufficient dosage, produce syndromes that include features of atropine intoxication. 

Franke, U. Munk, A. Wiese, M., Ionization constants and distribution coefficients of phenothiazines and calcium channel antagonists determined by a pH-metric method and correlation with calculated partition coefficients, J. Pharm. Sci. 88, 89-95... 

Interestingly, penicillamine—a degradation product of penicillin and phenothiazines—the histamine H,—receptor antagonists, such as promethazine teoclate, methadilazine hydrochloride, trimeprazine tartrate are found to increase the cholesterol levels. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

It also seems plausible that antipsychotic drugs competitively bind with dopamine receptors and block the action of dopamine on corresponding receptor sites, thus lowering psychotic activity. Central dopamine receptors are subdivided into Dj, D2, and according to some sources, Dj receptors. These receptors have a high affinity for dopamine, but they differ in sensitivity to neuroleptics of various chemical classes. For example, drugs of the phenothiazine series are nonselective competitive Dj and D2 antagonists. Unlike phenoth-iazines, antipsychotics of the butyrophenone series such as haloperidol display selective action only on D2 receptors. 

Phenothiazine derivatives are nonselective, competitive Dj and D2 antagonists that block dopamine activity on corresponding receptor sites. In addition, their action is... 

Ophthalmic beta blockers may affect oral beta blockers, catecholamine-depleting drugs, calcium antagonists, digitalis, and phenothiazines. 

Uses Allergic Rxns itching Action Phenothiazine antihistamine serotonin antagonist Dose Adults. 4-20 mg PO qSh max 0.5 mg/kg/d Feds. 2-6 y 2 mg bid-tid (max 12 mg/24 h) 7-14 y 4 mg bid-tid in hepatic impair Caution [B, ] BPH Contra Neonates or <2 y NAG BOO acute asthma GI obst Disp Tabs, syrup SE Anticholinergic, drowsiness Interactions T Effects Wf CNS depressants, MAOIs, EtOH X effects OF epi, fluoxetine EMS Use other CNS depressants w/ caution concurrent EtOH use can T CNS depression higher epi doses may be needed if used OD May cause mood changes, Szs, CNS depression, or CNS stimulation symptomatic and supportive... 

Many of these drugs have effects that are not mediated by Hi-receptors (Table 38.2). The antimuscarinic activity of several first-generation Hj-blockers may account for their effectiveness in combating motion sickness and their limited ability to suppress parkinsonian symptoms. The phenothiazines have some capacity to block a-adrenoceptors, whereas cyproheptadine Periactin) is an antagonist at serotonin receptors. Diphenhydramine Benadryl), pyrilamine (Ryna), and promethazine Phen-ergan) are effective local anesthetics. Many second-generation antihistamines also have been found to inhibit the non-histamine-mediated release of various... 

Phenothiazines are also nonspecific dopaminergic antagonists and are an old family of neuroleptics. However, they are less and less used (fluphenazine, oxa-flumazine, trifluoperazine, triflupromazine). Flupenthixol and isofloxythepine are recent neuroleptics that can be grouped with phenothiazines (Figure 8.29). 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Adrenergic blocking effect antagonists, specially of phenothiazine subgroups have weak alpha-receptor blocking effect. 

Chemically, it is a phenothiazine derivative and has equal potency at both Hj-histamine and 5-HT receptors as an antagonist. As H -histamine antagonist it has been used in various allergic conditions. It increases the appetite and promotes weight gain. 

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