Antihistamines cyproheptadine

To anticipate briefly, shortening the length of the side chain in the phenothiazines from three to two carbon atoms changes I he activity of the products from neuroleptics to antihistaminic iigents. A rather similar effect is seen in the tricyclic antidepressants. Reaction of ketone, 27, with the Grignard reagent I rom 4-chloro-l-methylpipyridine (35) affords the tertiary alco-liol, 36. Dehydration gives the antihistamine, cyproheptadine (37). ... 

Formation of lactam metabolites also has been reported to occur to a minor extent for the antihistamine cyproheptadine (Periactin)" -and the antiemetic diphenidol (Vontrol). "... 

Coadministration of the antihistamine cyproheptadine or other 5-HT antagonists with SSRIs might be expected to result in a pharmacodynamic interaction (i.e., reduced effectiveness for the SSRI). Cyproheptadine acts to block postsynaptic 5-HT. Lack of antidepressant efficacy has been reported when cyproheptadine was given concurrently with fluoxetine and paroxetine. 

The alleged interaction between the MAOIs and antihistamines appears to be based on a single animal study, and is probably more theoretical than real The exception seems to be cyproheptadine, which can reduce the effect of MAOIs because of its serotonin antagonist effect, see MAOIs or RIMAs + Antihistamines Cyproheptadine , below. 

Direct information about this interaction appears to be limited to these studies although cyproheptadine has also been found to oppose the antidepressant effects of MAOIs (see MAOIs or RIMAs + Antihistamines Cyproheptadine , p.ll31). One study suggests that not every patient is affected. If concurrent use is thou t appropriate, the outcome should be very well monitored for evidence of a reduc antidepressant response. 

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

Cyproheptadine (Periactin). Cyproheptadine is an antihistamine, commonly used to alleviate allergy symptoms, that also has serotonin-blocking properties. It has been successfully used to stimulate appetite in patients with medical illnesses such as cancer or AIDS. Cyproheptadine provides a small but measurable benefit in the rapidity of weight gain during the refeeding of patients with the restricting subtype of AN. However, bulimic subtype patients apparently fare worse with the addition of cyproheptadine. 

First-generation antihistamines Flypersensitivity to specific or structurally related antihistamines newborns or premature infants nursing mothers monoamine oxidase (MAO) therapy pregnancy (hydroxyzine) angle-closure glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction, elderly, debilitated patients (cyproheptadine). 

Of antihistamines like cyproheptadine, which also have antiserotoninerge properties, it was suggested on the basis of some clinical observations that they could bring forward an increased appetite and related increases in body weight. However, controlled comparative investigations in respect of these effects are missing. 

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... 

Anticholinergics and antihistamines chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), hydroxyzine (Vistaril and Atarax), cyproheptadine (Periactin), promethazine (Phenergan), dexchlorpheniramine (Polaramine) All nonprescription and many prescription antihistamines may have potent anticholinergic properties. Nonanticholinergic antihistamines are preferred in elderly patients when treating allergic reactions. High... 

Cyproheptadine is an antihistaminic 5-HT antagonist that has shown limited utility in reducing trau-... 

Cyproheptadine resembles the phenothiazine antihistaminic agents in chemical structure and has potent H receptor-blocking as well as 5-HT2-blocking actions. The actions of cyproheptadine are predictable from its histamine and 5-HT receptor affinities. It prevents the smooth muscle effects of both amines but has no effect on the gastric secretion stimulated by histamine. It also has significant antimuscarinic effects and causes sedation. 

There are some prophylactic treatments which are very individualized. Propanolol (p-blocker) has been used at 80-160 mg/day for up to 12 months. Methylsergide and dihydroergotamine(DHE), relatives of ergotamine, are used but have some serious side effects. Antihistamines such as cyproheptadine (Periactin ) have also been found to have tryptaminergic and anticholinergic activity in the CNS and can be used prophylactically. Calcium channel blockers have also been mentioned in an experimental vein. 

Cyprino-purple C2 occurrence, 3, 323 Cyproheptadine as antihistamine, 1, 177 metabolism, 1, 237 Cyproquinate... 

Two brief examples are presented to illustrate structure-activity problems for which this approach might be useful. The first example (Fig. 16) finds the similar structural features among five structurally diverse antihistamines (diphenhydramine, methapyrilene, cyproheptadine, dimethindene and promethazine). 

Fig. 16. Similar structural feature among five antihistamines (diphenhydramine, methapyrilene, cyproheptadine, dimethindene and promethazine)...

Although sedative antihistamines do not potentiate the effect of alcohol, they should be avoided in excess quantity. Overdose of astemizole can be treated with gastric lavage and supportive measures.86 Coadministration of astemizole and ter-fenadine with antiarrhythmics, antipsychotics, cisapride, and diuretics should be avoided. Chlorpheniramine maleate has been found to be incompatible with phe-nobarbitone sodium, kanamycin sulfate, and calcium chloride. Cyclizines have been used alone or with opioids in tablets or in injectable form for euphoric effects. Cyproheptadine has shown dependence in long-term use. Diphenhydramine is reported to be incompatible with amphotericin, cephalothin sodium, and hydrocortisone sodium succinate. Diphenhydramine and pheniramine maleate are sometimes used as drugs of abuse. Studies have shown that promethazine is adsorbed onto glass, plastic containers, and infusion systems.87... 

NITRATES 1. ANALGESICS-nefopam 2. ANTIARRHYTHMICS -disopyramide, propafenone 3. ANTIDEPRESSANTS-TCAs 4. ANTI EMETICS-cydizine 5. ANTIHISTAMINES -chlorphenamine, cyproheptadine, hydroxyzine 6. ANTIMUSCARINICS -atropine, benzatropine, cydopentolate, dicydover-ine, flavoxate, homat-ropine, hyoscine, orphenadrine, oxybutynin, procyclidine, propantheline, tolterodine, trihexyphenidyl, tropicamide. 7. ANTI-PARKINSON S DRUGS-dopaminergics 8. ANTI-PSYCHOTICS - pheno-thiazines, clozapine, pimozide 9. MUSCLE RELAXANTS-baclofen 1. t risk of antimuscarinic side-effects when isosorbide dinitrate is co-administered with these drugs 2. 1 efficacy of sublingual nitrate tablets... 

---