Ipecac alkaloids emetine

In addition to the above natural products, the ipecac alkaloid, emetine (6, chapter 15) and the antibiotic paromomycin (18, chapter 15), which are primarily used as antiprotozoal drugs, have also been found to be effective in the chemotherapy of trematode infections in humans. 

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. 

The most widely used emetic is syrup of ipecac, containing the alkaloids, emetine and cq haeline. Emetine induces vomiting by activation of sensory neurons in the vagus and sympathetic nerves to the stomach and centrally in the medulla, possibly at the CTZ. The release of serotonin and SP may be involved as 5-HT3 and NKi receptor antagonists prevent emesis induced... 

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. 

The antidiarrhoeal drug ipecac, which was introduced into Europe from Brazil in 1658, contains the amoebicidal alkaloids emetine (12) and cephaeline. Emetine remained the major remedy for amoebic dysentery and amoebic hepatitis for many years. Cephaeline is less active and more toxic. ( j-2-Dehydroemetine, which is made by synthesis, is equiactive with (—)-emetine and less toxic, but other chemical modification has not yielded better amoebicides. From investigations of synthetic routes to the benzoquinolizine moiety the tranquilizer tetrabenazine (13a) was discovered. The very similar compound benzquinamide (13b) is also a tranquilizer and antiemetic. 

When the heart can no longer pump an adequate supply of blood to meet the metabolic needs of the tissues or in relation to venous return, cardiac failure may ensue. The causes of cardiac failure are complex, but stem from mechanical abnormalities (e.g., pericardial tamponade), myocardial failure (e.g., cardiomyopathy and inflammation), and arrhythmias. In high-output failure, the cardiac output, which may be normal or even higher than normal, is not sufficient to meet the metabolic requirement of the body. Cardiac failure may predispose a patient to congestive heart failure, which is a state of circulatory congestion. Toxic injury, caused by agents such as doxorubicin, the alkaloid emetine in ipecac syrup, cocaine, or ethyl alcohol, is another way by which the functional integrity of the heart may also be compromised. 

Ipecac is the root of Cephaetis ipecacuanha, or of C. acuminata, a perennial shrub growing in Brazil and other South American states (Figure 44.1). It contains three alkaloids — emetin, cephaelin, and psychotrin. The dose of the powdered drug as an expectorant is from 1/2 to 2 grain (0.03 to 0.13 g) as an emetic, 15 to 30 grain (1.0 to 2.0 g) (Table 44.1). 

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. 

Emetine [EM e teen] and dehydroemetine [de hye dro EM e teen] are alternate agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation1. Intramuscular injection is the preferred route. Emetine is concentrated in the liver where it persists for a month after a single dose. It is slowly metabolized and excreted and can accumulate. Its ty2 is 5 days. The use of these ipecac alkaloids is limited by their toxicities. Dehydroemetine is probably less toxic than emetine. Close clinical observation is necessary when these drugs are used. Among the untoward effects are pain at the site of injection, transient nausea, cardiotoxicity (e.g., arrhythmias, congestive heart failure), neuromuscular weakness, dizziness, and rashes. 

Emetine in A Emetine in B Cephaeline in A Cephaeline in B Psychotrine in A Alkaloids in A Ipecac alkaloids in B Emetine Emetine in A Emetine in B Emetine in C Cephaeline Cephaeline in A Cephaeline in B Emetine Emetine Emetine in B Ipecac alkaloids in B Emetine Emetine in A Emetine in B Cephaeline Emetine Emetine in A Emetine in B Cephaeline in A Emetine Emetine in B Emetine in C Cephaeline... 

Emetine and Dehydroemetine. Tlic alkaloids emetine and dehydroemetine are obtained by separation from extracts of ipecac. They occur as Icvorotatnry. light-.sensitivc white powders that are insoluble in water. The alkaloids readily farm water-soluble salts. Solutions of the hydnx hlo-ridc salts intended for intramu.scular injection shnuld be adjusted tn pH 3.5 and. stored in light-resistant containers. 

Ipecac alkaloids were extracted and analyzed by HPLC as previously reported [section 1.2]. Two flasks were used for each culture condition. The contents of isoquinoline alkaloids, protoemetine, cephaeline and emetine in the transformed roots, are shown in Fig. (54). 

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. 

The active ingredients are the bisbenzyliso-quinoline alkaloids emetine and cephaehne which occur in the whole plant highest concentrations are in the roots with less in the stem and least in the leaves. The ratio emetine ce-phaeline is generally 2 1 in Matto Grosso Ipecac and 1 1 in Costa Rica Ipecac. 

A 10 mL sample of Ipecac was treated as in Experiment 15. For the titration, 5.00 mL of0.1500 N H2SO4 was added, which then required 31.60 mL of 0.025 N NaOH to reach the endpoint. The blank was 2.20 mL. How many mg of Ipecac alkaloids, calculated as emetine, were present This bottle had the same label as that in the example calculation. What are your conclusions ... 

Emetine and Related Alkaloids.—A review on the ipecac alkaloids has ap-peared. (— )-Alangiside (208) is a terpenoidal lactam recently isolated from Alangium lamarckii Thw. (Alangiaceae). The structure was proven by chemical correlation with desacetylipecoside (209) (Scheme 13). ... 

Inspection of the empirical formulas indicates a close relation between the Ipecac alkaloids which chemical study was soon to verify. Much of the early work on emetine was subsequently shown to be erroneous because the starting material was impure. The free alkaloid is amorphous but well characterized salts, especially the hydrobromide and the hydriodide, are obtainable. 

After a comparative investigation of the Ipecac alkaloids and some of their derivatives. Dale and Dobell (87) concluded that emetine acts through the host rather than on the parasite, that is, changes in the blood render it amebicidal (88, 89). Satisfactory cultural methods in vitro, which permit pharmacological investigations (90-93) and clinical tests (94, 95, 96), have been devised. 

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-... 

Ipecac symp is an alkaloid derivative of the ipecacuanha plant (Cephaline ipecacuanha). The principal alkaloids, emetine and cephaeline, both have emeto-genic properties. The emetine extract has been used for the treatment of amebiasis. Syrup of ipecac is widely available over the counter as an effective, rapidly acting emetic agent. Presently, the major source of poisoning is chronic intoxication resulting from intentional misuse by patients with eating disorders. Cases of Munchausen s syndrome by proxy, in which a parent repeatedly administers ipecac to a child, have also been reported. 

The Ipecac alkaloids, e.g. emetine (121), are reported to have their genesis through desacetylipecoside (120). ° This biogenesis results in the inversion of configuration at C-5 of (120) and, in the light of the discussion above on terpenoid indole bases, is being re-examined. [The stereochemistry of (120) follows unambiguously from an X-ray analysis of 00-dimethylipecoside. ° ]... 

The individual A. or their parent N-bases often derive their names fijom the natural product (example tro-pane=parent base of atropine and of cocaine) or finm the plants in which the A. occur (example sola-nine, vincamine), and sometimes from their physiological properties, like, e.g. morphine (Greek. Morpheus = god of sleep) and emetine (emetic, see ipecac alkaloids). 

Q. is used in the food industry as a bitter principle, according to legal regulations brandies may contain up to 50 mg/L Q. as bitter component. Q. has a bitter taste even at a dilution of 1 60 000. In mammals Q. can effect a decrease in heart rate and, at higher concentrations, muscular convulsions and paralyses. The commercially available quassin is a mixture of quassin, neoquassin, isoquassin, and 18-hydroxy-quassin. Q. can be used as a substitute for emetine hydrochloride (see ipecac alkaloids). Some pentacyclic Q. have antiviral, antiparasitic, insecticidal, antifeedant, amoebicidic, and anti-inflammatory activities. 

Ipecac alkaloids [178, 195, 196] t Part of the structure of the ipecac alkaloids, e.g. emetine 6.281) and cephaeline 6.280) [heavy bonding in 6.280) is closely similar to the terpenoid fragment of the alkaloids just discussed (Section 6.6.2) the remaining atoms are accounted for by two phenethylamine units. Investigations which have paralleled those of the terpenoid indole alkaloids have established the origins of these alkaloids (see Scheme 6.50). Desacetylisoipecoside 6.277) is the key intermediate for 6.280)... 

Ipecac alkaloids are derived from the amino acid tyrosine and the monoterpene secologanin and are therefore termed terpenoid-isoquinoline alkaloids. They occur in the eudicot families Alangiaceae and Rubiaceae. Two species, Psychotria ipecacuanha (Rubiaceae) and Alangium lamarckii (Alangiaceae), have been investigated in detail with respect to their metabolites and biosynthesis of their alkaloids (Fujii and Ohba, 1998). Roots and rhizomes of P. ipecacuanha are the source of cephaeline and emetine (Fig. 9), two compounds with emetic, expectorant, and amebicidal properties. 

The finding of emetine (see Volume VII, p. 419) ia Spermacoce verti-cillata L. (Borreria verticillata Mey.) (Rubiaceae) 125) occasions no surprise but to find the Ipecac alkaloids in Allangium lamarkii Thw. (see Volume VII, p. 509), a plant now relegated to Alanginaceae, is a remarkable example of parallel evolution in plants w hich can be only remotely related 126). 

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