the diaphragm. Many curare alkaloids have to be injected as they are not absorbed from the intestine and the injection produces a short-lasting reversible effect as the concentration of the alkaloids in the plasma is reduced by half every 13 min. A secondary effect of the curare alkaloids is the lowering of the arterial blood pressure, caused in some cases through the liberation of histamine and in others by ganglionic blockade. In small doses the curare alkaloids provide the muscular relaxation needed in abdominal and thoracic operations, in endoscopy and in painful spasmodic conditions found in tetanus and strychnine poisoning (Burgen and Mitchell, 1972; Lechat et al., 1978). The relaxation spreads down from the head to the abdomen and members and affects the diaphragm last. However, on complete relaxation of the abdominal muscles already 50% of the respiratory muscles are involved. Hence the use of these blockers requires ventilation and precautions (Lechat et al., 1978).

Curare-like compounds act as antagonists to acetylcholine by competing for the acetylcholine receptors, but other forms of curare can be acetylcholine-mimetic occupying the actual site of acetylcholine on the neuromuscular junctions and these forms are slowly destroyed by cholinesterase (Lechat et al., 1978).

Some of the South American, Japanese and Indian species of the Menispermaceae are the chief sources of curare alkaloids. They have been used as arrow or hunting poisons and were prepared in pots or bamboo tubes according to the region, as opposed to Strychnos curare, which was prepared in calabashes and is more toxic. The main alkaloids of curare are asymmetric bis-benzylisoquinoline (or bis-coc-laurine) alkaloids such as (-t-)-tubocurarine, stereoisomeric (—)-chondrodendrine, ((—)-bebeerine = buxine = pelosine) and also (+)- and (—)-isochondrodendrine, chondrofoline and oxyacanthine. Of all these, (-t-)-tubocurarine appears to be the most important and the South American Chondrodendrons remain its main source.

Most of the West African members of the Tricliseae and Cocculeae tribes contain curare alkaloids derived from bis-benzylisoquinoline, although not in large amounts. Cissampelos owariensis, C. mucronata, Cocculus pendulus, Tiliacora dinklagei, Triclisia dictyophylla and Epinetrum cordifolium have all been shown to have neuromuscular blocking action.

Erythrina alkaloids, with the exception of erythroidine, have neuromuscular blocking and CNS depressant and smooth muscle relaxant activities. They have the advantage of being active if taken orally but their action is short-lasting as they are tertiary bases and lose part of their activity through transformation into quaternary bases (which are 10-12 times less active). Their toxicity is high, however, and they have therefore now been mostly replaced by other drugs. West African Erythrina spp. with active constituents are E. senegalensis, E. excelsa and E. sigmoideae. Curariform activity is also reported in two further Fabaceae, Mucuna pruriens and Desmodium gangeticum.

Cissampelosmucronata A. Rich. syn. (C ■ pareira oi¥.T.h.) MENISPERMACEAE Velvet leaf

Cissampelos owariensis Beauv. ex DC. syn. (C. pareira L. var. owariensis (Beauv. ex DC.) Oliv., C. robertsonii Exell.) (Fig. 3.3) Pareira brava

L The roots of both species (which are often confused) are used locally as an emmenagogue, abortifacient, antipyretic and diuretic. A decoction of the leaves is used as a light purge. In India, the leaves are used as a local application for itch (Oliver-Bever, 1968). The roots of C. owariensis are known in commerce as Par err a brava.

C Fliickiger and his co-workers isolated from the roots of C. owariensis, 0.5% of the alkaloid bebeerine, which was later separated into two stereoisomeric forms and a neutral crystalline substance, deyamitine (Oliver-Bever, 1968). The alkaloids of the West African C. owariensis were examined by Dwuma Badu etal. (1975a), who have reported dehydrodicentrine, dicentrine, cycleanine, insularine and isochondroden-drine. In Portuguese Africa, Ferreira et al. (1965) isolated from the roots of C. mucronata, isobebeerine ((+)-isochondrodendrine), hyatine ((±)-bebeerine) and hyatinine. In India, hyatine and hyatidine (±)-4'-0-methylbebeerine) and curine ((—)-bebeerine) were also found in the local C. mucronata, and in total eleven quaternary and five tertiary alkaloids were detected (Srivastava and Khare, 1964; Boissier et al., 1965; Bhatnagar and Popli, 1967; Bhatnagar et al., 1967; Roychoudhury, 1972).

P The curarizing activity of C. mucronata was tested on toad recto-abdominal striated muscle and on rat isolated nerve-diaphragm preparations of rats (Correia da Silva and Pavia, 1964). Some curarizing action was observed, which was greater in the methachloride and methiodide derivatives of hyatine. Hyatine methiodide was 2.5 times more active than (+)-tubocurarine. The activity of the hyatine derivatives on blood pressure and respiration was greatest in those with the highest curarizing

Fig. 3.3. CissampelosowariensisBeauv. ex DC.

Fig. 3.3. CissampelosowariensisBeauv. ex DC.

f potency and decreased in parallel with the neuromuscular activity (Pradhan and De, 1959; Sen and Pradhan, 1963; Bhatnagar et al., 1967, 1971; Basu, 1970). Another bis-benzyl isoquinoline alkaloid isolated from the bark of C. mucronata, cissam-pareine, was found to have significant and reproducible inhibitory action against human carcinoma cells of the nasopharynx in cell culture (Kupchan et al., 1965).

Cocculus pendulus (J. & G. Forst.) Diels syn. (C. leaeba (Del) DC., Epibaterium pendulum J.R. & G. Forst.) MENISPERMACEAE

L The small red fruits are used by the Arabs to make an intoxicating drink. The roots of the plant are used in Nigeria as an antipyretic and in Senegal as a cholagogue and diuretic (Dalziel, 1937; Kerharo and Adam, 1974).

C The roots contain a bitter principle, colombin, and three alkaloids, pelosine (Chopra et al., 1956), palmatine and sangoline (oxyacanthine) also found in Berberis (Beauquesne, 1938). Chemically, pelosine is believed to be identical with bebeerine or chondrodendrine, but slightly controversial opinions exist (Henry, 1949). Palmatine is a phenolic base belonging to the protoberberines whilst sangoline is a bis-benzylisoquinoline alkaloid. The stem and leaves contain, besides mineral elements such as potassium, sodium, magnesium, iron, aluminium, copper and zinc, two new bases, penduline of a biscoclaurine type and a bis-benzylisoquinoline alkaloid, an isomer of trilobine, cocsuline (Bhakuni et al., 1970; Gupta et al., 1970; Joshi et al., 1974; Bhakuni and Joshi, 1975). In addition to the tertiary phenolic alkaloids, the rhizome of Cocculus trilobus has been found to contain cocculine and cocculidine (Wada et al., 1967) and two erythrinan alkaloids, which were named coccutrine and dihydroerysovine (Ju-Ichi et al., 1978). The Chinese drug Hang-Fang-Chi is obtained from C. laurifolius, C. diversifolius and C. japonicus, which have alkaloids related to those of C. sarmentosus, C. trilobus and C. hirsutus. An insecticidal alkaloid, cocculidine, has been obtained from C. trilobus (Oliver-Bever, 1968).

P Colombin and palmatine have strong stomachic and bitter tonic action, and Cocculus root has been used as a tonic in a similar way to Chasmanthera root. The root extract had a relaxant and antispasmodic effect on the rat ileum and stimulated the uterus of the albino rat. Toxicity was low; up to 40 mg/kg given intravenously and 100 mg/kg given orally produced no toxic effects in rabbits and albino rats. A solution of the alkaloids has a cardiotonic action which is five times that of the total extract and is comparable to that of 50-100 /¿g of digoxin (Das et al., 1964). Sangoline produced long-lasting hypotension in dogs and, in doses of 0.1-0.2 g, clonic convulsions and death through paralysis of the respiratory centre in rabbits (Henry, 1949; Das et al., 1964). Palmatine has similar paralysing action and is also strongly hypotensive. An extract of the stems and leaves of Cocculus pendulus has a distinct anticancer action. In sarcoma 180 it produces a 60% reduction, and in Lewin's lung carcinoma, 50% reduction, of the number of tumours compared to control animals (Abbot et al., 1966). The extract also has an anticancer activity against human epidermal carcinoma of the nasopharynx in tissue culture (Bhakuni et al., 1969b).

Tiliacora dinklagei Engl. syn. (Glossopholis dinklagei (Engl.) Stapf)

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