As to the accompanying symptoms, it does not appear that successful antagonism necessarily brings with it, or implies any particular class of these. The antagonism may be attended by a greater prominence of the effects either of the atropia or of the physostigma, and no special action belonging to either of these two substances requires to be prominently and obviously produced in order that the antagonism shall be successful.

Therapeutic Action. - The earliest, and still the most frequent, use of Calabar bean, is in eye affections, as already described. But it has been used, with more or less success, in various nervous affections.

In Tetanus the results obtained by some observers have been so remarkable as to excite great hopes for the future treatment of that terrible disease; but there are very conflicting statements. Dr. Fraser has borne energetic testimony to its value,1 and Dr. Eben Watson2 has collected a considerable number of cases of its use, and shows that the majority recovered. Moreover, he gave enormous doses of the alcoholic extract: one patient, who recovered, took (in forty-three days) 1,026 grains, and as much as 72 grains in one particular twenty-four hours. He believes that the dangers of poisoning are to be avoided if care be taken to adapt each dose to the necessities of the moment, and to support and stimulate the patient freely. Mr. McNamara,3 of Calcutta, has also had excellent results in a large number of cases. On the other hand, many observers have tried the remedy in isolated cases of tetanus, with no good effect. In strychnia-tetanus' there is a case of recovery under Calabar bean recorded by Dr. Keyworth.4

In Chorea there is a considerable amount of evidence in favor of the bean, but it is scarcely needful to say that it is much more difficult to be sure that the remedy was the real cause of recovery in chorea than in tetanus. Harley,5 Ogle,6 and McLaurie,7 all testify favorably. Gubler,7 on the contrary, reports its failure in one case, and other persons have had similar negative results.

1 Practitioner, August, 1868.

2 Practitioner, April, 1870; Lancet, April 4 and 11, 1868; Glasgow Med. Journal, Nov.. 1868.

3 Practitioner, 1872.

4 Glasgow Med. Journal, Nov., 1868.

5 Med. Times and Gaz., Jan. 16, 1864. 6 Med. Times and Gaz., Sept. 2, 1868.

7 Commentaires de Therapeutique.

In Delirium Tremens Calabar bean has been tried a few times; but there were no good physiological grounds for expecting success, and it does not seem to have been obtained.

In Epilepsy, also, Calabar bean has been tried in a few isolated cases; but there is no positive evidence of any value, and it is not easy to see how the drug could be expected to do much, except, possibly, in a temporary manner, by reducing excited spinal reflex irritability. The latter condition, however, does not exist in the majority of cases of epilepsy.

In regard to the special applications of calabar-extract and of pure physostigmine to the treatment of eye affections, there are two or three matters that should be particularly mentioned. There is a large amount of evidence to show that Calabar bean directly stimulates the third nerve; this is proved by the evidence not only of the ophthalmic surgeons, but of Gubler. Mr. Wharton Jones1 states some facts which tend to show that physostigma contracts the circular fibres of the iris, and the veins, as opposed to atropia, which acts on the pupil through the sympathetic, and which contracts the arteries. From these actions it results that paralysis of the circular fibres and of accommodation, such as are liable to follow cold, or to follow diphtheria or other debilitating constitutional diseases, can be successfully treated with the bean; also excessive atropinization of the pupil can be neutralized (but as the action of the bean is rather fugitive, it needs to be repeated): again the pupil may be reduced in size for the purpose of shutting out the irritant effects of light upon an inflamed choroid or retina. It is generally employed, for ophthalmic purposes, in a topical manner.

Preparations And Dose. - Pure physostigmine is seldom used, being difficult to prepare; but Vee 2 recommends a solution of 1 in 2,000 or 1 in 1,000 of the sulphate of physostigmine for local use, one or two drops to be applied; for internal use, about 1/64 to 1/73 grain for a dose; for subcutaneous injection, about one-half of the latter quantities. But ophthalmists now most frequently employ the divided squares or discs of impregnated paper or gelatine, each one of which, when placed in the eye, is sufficient to produce the required effects. The dose of the bean itself is said to be from 1 to 4 grains, and of the pharmacopoeial extract, 1/16 to 1/4 grain or more; but the severity of the affection which we may have to deal with must be taken into consideration, and bad cases of traumatic tetanus may require (as shown by Dr. Eben Watson) an extremely frequent repetition of the dose, so that large quantities are taken in each twenty-four hours. The subcutaneous injection of calabar-extract should always be done in the manner recommended by Dr. Haining, viz. by mixing the dose with 10 to 15 minims of water, and neutralizing its acidity with carbonate of potash. But Dr. Eben Watson states that he has not found good results from the subcutaneous injection, and much prefers to give the drug either by the mouth or by the rectum.

One final remark must be made, as to the proper manner of using physostigma in cases of poisoning by belladonna or atropia. The dose and repetitions must be regulated of course in great part by the apparent effects upon the pupil; but it must be remembered that there are two actions of physostigma, the more formidable of which is its tendency, in large doses, to paralyze the heart. Very close watch must therefore be kept on the circulation, and the remedy should be given in fractional doses, repeated as often as is found necessary and safe. (Phillips.)

1 Practitioner, Sept., 1869.

2 Recherches Chim. et Physiol, sur la Feve de Calabar. Paris, 1865.