THE PHARMACOLOGICAL ACTION OF TUTU. 291 



earlier convulsions usually commence in a tonic spasm. The animal presents a 

 frightened appearance, the muscles of the limbs increase in tone and become rigid, 

 and opisthotonos develops. This tonic spasm terminates in a clonic one, which in 

 turn ends in exhaustion. During the convulsion, respiration is absent, and it may not 

 return until the period of exhaustion has lasted for two minutes or more. A few 

 minutes later the animal sits up and appears normal. This alternation of convulsions 

 and exhaustion with a normal appearance may occur many times ; but after a few 

 convulsive attacks, clonic movements of the limbs, usually accompanied by retraction 

 of the head, generally become constant. Salivation, dilatation of the pupils and of 

 the vessels of the ears, are frequent symptoms. Death may occur in the first or a 

 subsequent convulsion, or may result from exhaustion. 



After non-lethal doses the convulsions are generally less severe but more character- 

 istic. There is, at first, usually an appearance of clinging to the ground, often 

 accompanied by muscular tremors, and the gait becomes hesitating and spasmodic ; 

 but the convulsions themselves commence with twitches about the eyes or mouth, or 

 with erection or retraction of the ears, and extend to the whole head and fore part 

 of the body. Frequently these movements rapidly terminate, especially in the earlier 

 attacks, in a tonic convulsion ; but later the convulsions are almost solely clonic. At 

 this period, most frequently in animals which have been given a relatively small dose, 

 a curious series of movements often occurs. The animal commences to push backwards 

 with its forefeet, the hind parts being kept fixed, until it may, when the whole move- 

 ment is carried out, perform a somersault over its tail. The movement may be 

 abandoned at any point, and the animal may remain in the constrained position or 

 assume a normal attitude. The movement may also be preceded, or accompanied in 

 its early stages, by clonic spasm of the face or head, and it may terminate after the 

 somersault in a convulsion. Christie mentions somersaulting round a transverse axis 

 in the protocol of one of his experiments on cats. 



Tooted rabbits frequently lay, often for long periods, with the hind limbs more or 

 less outstretched and with toes outspread as in the final stages of a spring. This 

 position was so common that I termed it " characteristic position." 



Doses which do not produce convulsions have an effect on the medullary centres 

 which will be described later. 



The lethal dose* for rabbits is about 0'0025 grm. tutin per kg. body-weight 

 administered by hypodermic injection. After such a dose, death usually occurs from 

 exhaustion. The lethal dose cannot be determined with exactitude, as it varies some- 

 what with external influences. Thus a dose which is usually non-lethal may be 



* In a "Report on the Physiological Action of Tutin" by Dr Fitchett and Professor Malcolm, published in the 

 Annual Report of the New Zealand Department of Agriculture for 1908, which has reached me since the above was 

 written, the minimal lethal dose of tutin by hypodermic injection (unless otherwise stated) is given in mg. 

 per kg. body-weight as follows : — cats, 0'75 ; guinea-pigs, 2 ; rabbits, 2 - 5 ; lizards, 3-4 ; birds, 10'5 (by oral adminis- 

 tration) ; frogs, 10 - 5 ; fishes, 50 (when immersed in the solution). An extended report by Fitchett and Malcolm has 

 appealed as this paper is passing through the press (see note at end). 



