Histamine agents

Ito, C., Onodera, K., Watanabe, T., and Sato, M. (1997). Effects of histamine agents on methamphetamine-induced stereotyped behavior and behavioral sensitization in rats. Psychopharmacology (Berl) 130(4), 362—367. 

Parrot J-L, Wyczolkowska A, Santais MC, Ruff F (1974) The action of nicotinamide on the release of histamine. Agents Actions 4 202 Pauling L (1968) Orthomolecular somatic and psychiatric medicine. J Vital Subst Dis Civiliz 14 1... 

Fantozzi, R., Brunelleschi, S., Giuliattini, L., Blandina, P., Masini, E., Cavallo, G., and Mannaioni, P. F., 1985, Mast cell and neutrophil interactions A role for superoxide anion and histamine, Agents Actions 16 260-264. 

The market for antiulcer agents (Fig. 1) is large and is comprised of both prescription and over the counter (OTC) products. The estimated prescription market is over 3 biUion aimuaHy in the United States, whereas the more difficult to estimate OTC market is in the range of 500 million aimuaHy. Several pharmaceutical companies are attempting to obtain approval for OTC use of prescription-only agents, and patent protection for several of the histamine antagonists mns out in the mid-1990s. 

Clinically Efficacy. It is evident from the mechanism of action of antihistamines and the etiology of allergic diseases that antihistamines in no sense achieve a cure of the patient s allergy. After the adrninistration of a therapeutic dose, a temporal blockade of the effects of histamine is obtained. Whereas classical antihistamines needed at least twice daily adrninistration, for most of the more recently introduced agents adrninistration once daily is sufficient. 

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

From 1981 to 1995 other dmgs switched to OTC were the antifiingal preparations containing micona2ole nitrate [22832-87-7] (7) and clotrima2ole [23593-75-1] (8) the antiinflammatory agent ibuprofen [15687-27-1] (9) and the histamine H2-receptor antagonists famotidine [76824-35-6] (10) and cimetidine [51481-61-9] (11). 

FLUORIMETRIC DETERMINATION OE HISTAMINE WITH o-PHTHALDIALDEHYDE IN THE PRESENCE OE REDUCING AGENTS... 

Several methods were reported for the analysis of histamine, but the fluorimetric determination with o-phthaldialdehyde (OPA) the most widely used. It was shown that adducts, formed in the reaction of histamine with OPA in the presence of reducing agent, is more stable and gives high relative fluorescence intensity. The influences of different tiols on the fluorimeric determination histamine with OPA have been investigated. 

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet "antihistamines." This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

Etintidine (84), an imidazole-containing histamine H-2 receptor antagonist, is an antiiilcer agent conceptually related to cimetidine and ranitidine. It can be synthesized by various routes one of which terminates by an addition-elimination reaction of propargylamine with substituted N-cyano-S-methylisothiourea derivative 83 to give etintidine (84) [28]. 

Kenakin, T. P., and Cook, D. A. (1976). Blockade of histamine-induced contractions of intestinal smooth muscle by irreversibly acting agents. Can. J. Physiol. Pharmacol. 54 386-392. 

Antacids are neutralizing agents. Examples are magnesium hydroxide, magnesium trisylicate and aluminium hydroxide. Prior to the introduction of histamine-H2 receptor antagonists and proton pump inhibitors, they were the standard drugs for the treatment of duodenal/ peptic ulcers. Today their clinical use is limited to the treatment of dyspepsia and the symptomatic relieve for patients with peptic ulcers. 

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