Histamine pilocarpine

L-histidine Imidazole alkaloids Imidazole Histamine Pilocarpine Pilosine... 

Imidazole (glyoxaline) is the principal nucleus in histamine from ergot and pilocarpine from pilocarpus (Figure 11.6). 

The administration of morphine is followed by a series of complex events. Analgesia, euphoria, addiction, and respiratory depression are stressed in the literature, but if morphine had only its effect on carbohydrate metabolism it would rank wdth insulin and phloridzin in interest if it had only its effect on smooth muscle it would rank with pilocarpine and physostigmine and if it had only its effect on gastric secretion and salivation it wmuld rank with histamine. But consideration of some effects is lost in the importance of analgesia and only possible counter indications to its use as an analgesic remain continuously on the experimental horizon. 

These two substances abolish the spasm caused by histamine and pilocarpine on the lungs in situ) of dogs. But again it is 3000 times less active than adrenaline. Their action is purely peripheric in nature, acting directly on smooth muscle (204). 

A thin-layer electrophoretic method for separation of pilocarpine from drug sources has been developed. Other recent analytical methods used for the determination of pilocarpine include t.l.c., potentiometry with ion-selective membrane electrodes,and photodensitometry. Histamine (7) has been found not to be active at the water-air interface by electric-potential and surface-tension measurements of aqueous solutions of the alkaloid. ... 

In our Konzett assay, ll-deoxy-16-methyl derivatives showed exceptionally high potency (48), an observation also made by a Wyeth group (113). However, Turther examination of 11-deoxy-16(R/S)-methyl-PGEi (XXIV) in the pilocarpine dog assay indicated this compound to be relatively ineffective and of no interest. Another member of this series, 16(S)-methyl-20-methoxy-PGE2 (XXV, YPG-209), has been reported to be 230 times as potent as PGE2 in the guinea pig vs. histamine-induced spasms. It also is claimed to be orally effective in this model without concommitant hypotension or diarrhea (169). This is the first claim, that we are aware of, for oral activity for any prostaglandin bronchodilator and we await the results of further studies with this compound. 

This group of alkaloids is an exception in the transformation process of structures, because the imidazole nucleus is already made at the stage of the precursor. The a of these alkaloids is L-histidine, and the first A is developed in a decarboxylation process by histidine decarboxylase (HDC). The histamine is a product of this reaction (Figure 2.38). Other alkaloids from this group include, for example, dolichotheline, pilocarpine, and pilosine. 

Only a very limited number of alkaloids derived from histidine are known. As an example of these alkaloids, (+)-pilocarpine is described in this chapter, as well as histamine. Alkaloids derived from histidine are also called imidazole alkaloids because of the imidazole nucleus in the histidine skeleton. 

Histamine possesses hormone activity in animals (E 3.1) and acts as a neurotransmitter (E 3.2). It is a plant feeding deterrent present, for instance, in nettle toxin (E 5.5.3). Also the alkaloid pilocarpine has strong physiological activity in vertebrates and deters potential predators (E 5.5.3). It is used as a cholinergic drug in medicine (F 2). Urocanic acid, hydantoin propionic acid, imidazoleacetic acid riboside, 1-methylhistidine, 1-methylimidazoleacetic acid and other imidazole derivatives are involved in the removal of L-histidine and histamine residues from the organism of animals. They are found in the urine. Urocanic acid is also a constituent of sweat (E 1). It is involved in the protection of skin to UV radiation (E 2.2). 

Parietal secretion is evoked by histamine injection, and is essentially an isotonic solution of HCl, approximating in value to 0-1 N, or 0-365 per cent. Non-parietal secretion is evoked by pilocarpine injection, and is rich in nitrogenous solutes and neutral chloride, but poor in free HCl. As collected, gastric juice may have a concentration of HCl up to 0-1 N, in man and 0 17 N, in dogs. The pH range is 1-1-1-8. 

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