Cephaelis ipecacuanha Ipecac alkaloids

Rubiaceae, such as Cephaelis acuminata, Cephalis ipecacuanha, or Cephaelis accuminata. Ipecac alkaloids have powerful emetic and expectorant properties as well as anti-amoebic and antitumor activity, and some of them are widely used to treat amoebic dysentery (e.g., emetine and tubulosine), as well as schistosomiasis, leishmaniasis, and malaria (e.g., emetine). Isoquinoline alkaloid crispine A exhibits cytotoxic activity against SKOV3, KB, and HeLa human cancer lines and was isolated from C. crispus by Zhao et al. ... 

Ipecac is prepared from the dried roots and rhizomes of Cephaelis ipecacuanha (Brot.) A. Rich, and contains the alkaloids emetine [483-18-1] (17) and cephaeJine [483-17-0] (18) in a ratio between 2 1 and 4 1. It has been used extensively in cough preparations and is beheved to act by gastric reflex stimulation. Toxic effects include vomiting, irritation of the gastrointestinal tract, and cardiac arrhythmias (19). Ipecac symp is available over-the-counter in the United States only in 30-mL containers for use as an emetic in treating poisonings. 

Ipecac syrup is prepared from the dried rhizome and roots of Cephaelis ipecacuanha or Cephaelis acuminata, plants from Brazil and Central America that have the alkaloid emetine as their active principal ingredient. It acts directly on the CTZ and also indirectly by irritating the gastric mucosa. Ipecac is cardiotoxic if absorbed and can cause cardiac conduction disturbances, atrial fibrillation, or fatal myocarditis. If emesis does not occur, gastric lavage using a nasogastric tube must be performed. 

Avarol and avarone derivatives (from the Red Sea sponge Dysidea cinerea), the alkaloids psy-chotrine and O-methylpsychotrine (from ipecac, the dried rhizome and root of Cephaelis ipecacuanha), and phloroglucinol derivatives such as mallotojaponin, from the pericarps of Mallotus japonicus, have all been reported to inhibit the reverse transcriptase activity of HIV-1, noncom-petitively with respect to the natural substrate (dNTP). In neither case was the anti-HIV-1 activity determined in cell culture, so it is not clear whether any of these compounds is really an effective... 

Note The most commonly used emetics are ipecac and apomorphine. Induced emesis is the preferred means of emptying the stomach in awake patients who have ingested a toxic substance or have recently taken a drug overdose. Emesis should not be induced if there is central nervous system depression or ingestion of certain volatile hydrocarbons and caustic substances. Ipecac syrup is prepared from the dried rhizome and roots of Cephaelis ipecacuanha or of C. accuminata, plants from Brazil and Central America, in which the alkaloid emetine is its active principal ingredient. 

The close biogenetic relationship of the ipecac and monoterpenoid indole alkaloids has already been reviewed in several places (3,5,117,287). In the case of the ipecac alkaloids, tracer experiments (288) have shown that labeled geraniol (146) and loganin (148) are incorporated by Cephaelis ipecacuanha into radioactive cephaeline (149) and ipecoside (150). Thus, the C9-C,0 units of the ipecac alkaloid and ipecoside, represented by thickened lines in formulas 149 and 150, are of monoterpenoid origin from geraniol (145), and loganin (147) acts as a precursor for both alkaloids. The incorporation of glycine into the C9 unit of cephaeline (2) in Cephaelis plants has also been reported (289). 

Scheme 2. Biosynthesis of ipecac, Alangium, and indole alkaloids nitrogenous portion. Pathway (a) in Cephaelis ipecacuanha pathway (b) in Alangium lamarckii.

The monoterpene isoquinoline alkaloids are constituents of the genus Cephaelis and selected other Rubiaceae species. C. ipecacuanha (ipecac) is a powerful emetic whose active principle is emetine, derived through the condensation of dopamine and secologa-nin (Fig. 33). Emetine is also a powerful amebicide, antiviral, and inhibitor of protein synthesis. It is now largely replaced by synthetic dehydroemetine. 

Callus and adventitious roots of ipecac (Cephaelis ipecacuanha ) were induced on the leaf segments from axenic shoot culture and their capabilities for alkaloid production were investigated [15, 52]. 

A one-year-old Cephaelis ipecacuanha plant propagated through shoot-tip culture (section 1.1) in a greenhouse accumulated ca. 2 mg emetine and ca. 2 mg cephaeline, respectively, in its roots ca. 0.2 g total dry weight). On the other hand, the root culture of ipecac cultured for 7 weeks in 50 ml MS medium containing 0.01 mg/1 5,6-Cl2-IAA yielded almost the same amounts of alkaloids, 0.6 mg emetine and 2.4 mg cephaeline. Thus the root culture of ipecac is a realistic economic source of the isoquinoline alkaloids. 

Syrup of ipecac is available as a nonprescription product in many countries. It is derived from the dried rhizome and roots of the Cephaelis ipecacuanha or Cephaelis acuminata plant. These plants contain the potent emetic alkaloids emetine and cephaeline, which induce vomiting by both direct local gastrointestinal effects and central nervous system actions. Emesis following syrup of ipecac ingestion typically occurs within 20 min of ingestion and persists for 30-120 min. 

Emetine (Fig. 7-9) in the form of the crude drug obtained from the roots and rhizomes of Ipecac (Cephaelis ipecacuanha) has been in use since the seventeenth century. The alkaloid, as the hydrochloride, has been used parenterally to treat amebic dysentery. It is also effective in hepatic infestation, but not against amebic cysts. Because of its cardiac toxicity and emetogenic properties, it has been superseded by metronidazole and chloroquine, but it is still used as an alternative. The amebicidal mechanism of emetine is protein synthesis inhibition by interference of peptidyl-RNA translocation. Since this action is general to eukaryotic cells, its relative selectivity in the presence of mammalian cells is not well understood. Unrelated uses of Ipecac (presumably due to its alkaloid content) are as an expectorant in cough preparations and an emergency emetic (Syrup of Ipecac). 

Ipecac is a mixture of the alcohol-soluble alkaloid that is obtained from the South American plant Cephaelis ipecacuanha and is used solely in the form of syrup of ipecac. Apomorphine hydrochloride and copper sulfate are also emetics. Syrup of ipecac and copper sulfate cause emesis by locally irritating the stomach, whereas apomorphine stimulates the chemoreceptor trigger zone for emesis located in the caudal portion of the fourth ventricle (area postrema), which in turn stimulates the vomiting center in the lateral reticular formation of the medulla (see also Figure 73). 

Ipecac is a mixture of the alcohol-soluble alkaloid which is obtained from the South American plant Cephaelis ipecacuanha, and is used solely in the form of syrup of ipecac. Apomorphine hydrochloride and copper sulfate are also emetics. 

Ipecac Alkaloids.— The stereochemistry of ipecoside (71) is known by X-ray analysis, and this has been confirmed. Feeding experiments in Cephaelis ipecacuanha have given results which demonstrate that it is not desacetylipecoside (72), as previously supposed cf. ref. 2), but desacetylisoipecoside (73), with the same stereochemistry at C-1 (= C-llb) as cephaeline (76) and emetine (75), which is the true precursor for these alkaloids. Similar results were obtained for cephaeline (76) in Alangium lamarckii On the other hand, desacetylipecoside (72), and not (73), is the precursor for ipecoside (71) (in C. ipecacu-... 

Various groups of South American Indians used ipecac root long before their contact with Europeans. Ipecacuanha was brought to Europe late in the 17th century. This preparation is derived from the root of Cephaelis ipecacuanha (Rubiaceae). Ipecac (from Brazil) consists of about 2% alkaloids, 60-70% of which is emetine (111) and about 25% cephae-line (112) (Fig. 32.35). 

Ipecac is obtained from the dried rhizome and roots of Cephaelis ipecacuanha (Rubiaceae), a low bush indigenous to Brazil. Ipecac contains five isoquinoline alkaloids, including emetine, cephaline and psychotrine. Emetine hydrochloride is used as an antiprotozoal agent. Syrup of ipecac is an emetic and poison antidote. 

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