Physostigminae Salicylas. Physostigmine Salicylate, CHON. - CHO, U.S.P.

Physostigma venenosum, Balfour.  The salicylate of an alkaloid obtained from the dried ripe seed.

Habitat.  W. Africa (near mouths of Niger and Old Calabar Rivers, in the Gulf of  Guinea); introduced into India and Brazil.

Syn.  Calabar Bean, Ordeal Bean, Chop Nut, Split Nut; Physostigmatis Semina; Fr. Feve  de Calabar; Ger. Faba Calabarica, Kalabarbohne; Physostig. Salicyl., Eserine Salicylate;  Fr. Salicylate d'Eserine Salicylate; Fr. Salicylate d'Eserine; Ger. Physostigminum  salicylieum, Physostigminsalicylat.

Phy-so-stig'ma.  L. fr. Gr...., a bladder, + ..., stigma -- i.e., stigmatic appendage is  hollow and inflated.

Ven-e-no'sum.  L. venenosus, full of poison, poisonous -- i.e., plant's property.

Cal'a-bar Bean -- i.e., bean from the Calabar district on W. African coast.

Plant

Woody, perennial climber; stem 12-15 M. (40-50 degrees) long, 5 Cm. (2') thick, smooth; root spreading; leaves large pinnately trifoliate, leaflets 7.5-15 Cm. (3-6') long, ovate pointed; flowers purplish, racemes; fruit June-Sept., legume 10-17.5 Cm. (4-7') long, compressed, pale brown, 2-valved, dehiscent, inside woolly, 2-3-seeded.  Seed, oblong, ellipsoidal, somewhat compressed reniform, 15-30 Mm. (3/5-1 1/5') long, 10-15 Mm. (2/5-3/5') broad, 12 Mm. (1/2') thick, reddish, chocolate-brown, smooth, brownish-black groove, 2 Mm. (1/12') wide, extending almost the entire length of convex edge, margins of seedcoat on both sides of the groove somewhat elevated, brownish-red and thickened; 2 concavo-convex cotyledons; taste at first starchy, afterward acrid.  Powder, grayish-white -- numerous starch grains, fragments of seed-coat with thick cells resembling stone cells, occasional fragments with tracheae.  Embryo 72 p.c., integuments 28 p.c., the former when moistened with potassium hydroxide T.S. -- pale yellow; solvent: alcohol.  Dose, gr 1-4 (.06-.26 Gm.).

Adulterations

P. cylindrosper'ma, seed 4 Cm. (1 3/5') long, nearly cylindrical, groove and hilum shorter, not extending quite to the end; En'tada scan'dens, seed round, flat, 5 Cm. (2') broad (poisonous), also Elae'is guineen'sis, Oil Palm Seed, and seeds of Mucuna species, none of which resemble Calabar bean.

Commercial

Plant first noticed medicinally in 1846, and, except ligneous stem, resembles our Strong and Lima Beans (Phase'olus multiflo'rus and P. luna'tus), preferring banks of streams into which the fruit often falls only to be dispersed and conveyed to settlers more or less remote.

Constituents

Physostigmine (eserine) .1 p.c., eseridine, physovenine (strong myotic), eseroline, eseramine, CHON (crystalline physiologically inactive), calabarine (liquid, not yet obtained pure, antagonistic to physostigmine, tetanic, may cause diarrhea and convulsions, soluble in alcohol, water, insoluble in ether), phytosterin -- separable into sitosterin 80 p.c., stigmosterin 20 p.c., which crystallizes with 1 molecule of HO, inactive, starch 48 p.c., proteins (albumin) 23 p.c., gum, fat, ash 3-4 p.c.

Physostigmine, CHON. -- Chiefly in embryo; claimed to be a reduction product of geneserine, CHON, and is obtained by mixing powdered bean with 1 p.c. of tartaric acid, exhausting with alcohol, evaporating, treating residue with water, agitating filtrate with ether to remove color adding sodium bicarbonate, shaking with ether, evaporating, getting colorless, amorphous physostigmine; hygroscopic, liquefies at 45 degrees C. (113 degrees F.), tasteless, soluble in alcohol, ether, chloroform, benzene, carbon disulphide, slightly in water; forms salts (benzoate, citrate, hydrobromide, hydrochloride, nitrate, etc.).  With alkalies or chlorinated lime yields red rubreserine; with sulphuric acid gives yellow, then olive-green.  Dose, gr. 1/120-1/60 (.0005-.001 Gm.).

Physostigminae Salicylas.  Physostigmine Salicylate, CHON. CHO, U.S.P. -- Obtained by neutralizing alcoholic or ethereal solution of physostigmine with salicylic acid, allowing to crystallize; it is in colorless, faintly yellow, shining crystals, odorless, acquiring red tint on cold, saturated aqueous solution neutral or faintly acid, usually pink on standing.  Tests: 1. Aqueous solution with ferric chloride T.S.--deep violet color; solution of .1 Gm. + 2 cc. of sulphuric acid -- not darker than yellow within 5 minutes (abs. of readily carbonizable substances).  2. Evaporate .005 Gm. to dryness with a few drops of ammonia T.S. -- blue residue, which dissolved in alcohol, + acetic acid in excess--red, fluorescent solution; cold saturated solution 5 cc., + few drops of sodium hydroxide T.S. -- pink color rapidly develops; incinerate .1 Gm. -- ash negligible.  Impurities: Sulphate, readily carbonizable substances.  Should be kept dark, in small, well-closed containers.  Dose, gr. 1/120-1/60 (.0005-.001 Gm.).

Eseridine, CHON. -- By some thought to be calabarine, is a derivative of physostigmine, from which it differs by containing HO, and into which it can be converted by dilute acids; obtained from its mother-liquor by precipitating with lead subacetate and ammonia, evaporating filtrate, treating residue with alcohol, precipitating with phosphotungstic acid, decomposing with baryta; occurs in 4-sided crystals, soluble in alcohol, chloroform, ether, acts similar to physostigmine.  Dose, gr. 1/20-1/10 (.003-.006 Gm.).

PREPARATIONS (Unoff.).  SEED: Extract, gr. 1/10-1/2 (.006-.03 Gm.), Tincture, 10 p.c. (alcohol), mv-20 (.3-1.3 cc.).  Lamellae Physostigminae (Br. -- sulphate), 1/1000 gr. (.00006 Gm.).

Properties

Sedative, myotic, motor depressant, paralyzant, emetic, purgative, diaphoretic, sialagogue, poisonous.  Stimulates salivary, gastric, and intestinal secretions, peristalsis, acting directly upon the unstriped muscle-fibers, quickens breathing, then retards it, heart becomes slow and irregular, but more powerful, finally feeble and ceasing altogether, depresses, ultimately paralyzes spinal cord reflex, and motor centers.

Uses

Tetanus, chorea, epilepsy, progressive paralysis, tonic convulsions, gastralgia, strychnine and atropine poisoning, constipation (combined with belladonna and nux vomica).  Externally -- in neuralgia, muscular rheumatism, malignant tumors.  Physostigmine salicylate (1/2 p.c. in water, few drops into eye) for breaking up ocular adhesions (iris, cornea, lens), lessen intra-ocular tension, iritis, corneal ulcers, prolapsed iris, paralysis of the iris accommodation following diphtheria, glaucoma.  In Africa as ordeal bean of Calabar for punishing criminals and for witchcraft, the accused having to eat them until they vomit or die: if former, innocent; latter, guilty (?).  A paste of 20 seed will kill.

Poisoning

Have nausea, giddiness, abdominal pain, indistinct vision, diminished heart action, muscular tremors and weakness, then complete relaxation, retarded respiration, motor paralysis, sphincters contract, cold extremities, skin covered with cholera-like sweat.  Conscious until death, which is caused by carbon dioxide narcosis, and paralysis of the respiratory centers and heart-muscle.  Evacuate stomach (emetics pump); give atropine (physiological antidote) hypodermically, gr. 1/20 (.002 Gm.); tannin, chloral hydrate (spine), strychnine, diffusible stimulants, coffee, ammonia, digitalis, alcohol, artificial heat and respiration, electricity.  Empty bladder often (catheter, as the drug is eliminated by kidneys (bile and saliva), and urine becomes poisonous.

Incompatibles

Vegetable astringents, tannin, caustic alkalies, atropine, chloral hydrate, motor and tetanizing excitants.

Synergists

Motor depressants, conium, gelsemium, amyl nitrite, etc.