506 5. QUINONES 



EFFECTS IN THE WHOLE ANIMAL 



The pharmacological responses and the toxic patterns observed depend 

 on the type of quinone used, the species, and the dosage, among other 

 factors which will be considered in due course. Nevertheless, it is remarkable 

 that rather similar toxicities have been reported for many quinones and 

 species, and it is possible to present a general picture of the poisoning. 

 Whether this implies a common mechanism of action is, however, debatable. 

 The quinones have been used at one time or another in animals or man to 

 reduce body temperature, in hypertension to reduce the blood pressure, 

 in hypoprothrombinemic hemorrhagic conditions, in the prophylaxis and 

 suppression of malaria, for schistosomiasis, in various bacterial and fungal 

 infections, and as tumoristatic agents. Our purpose is to relate, whenever 

 possible, the effects observed on the whole animal or its organs with meta- 

 bolic disturbances. In the case of the quinones it is very likely that the 

 responses to be described are the result of interactions of these quinones 

 with enzyme systems, and yet it is difficult in a particular instance to 

 demonstrate conclusively a selective mechanism of action, due primarily 

 to the paucity of information available on the in vivo metabolic changes or 

 the alterations of metabolism in the tissues themselves. However, it is hoped 

 that, by presenting what is known of both sides of the picture, some corre- 

 lations may be made and the problems for the future more clearly defined. 



General Aspects of the Toxicity. 



It appears that the central nervous system is the earliest and most 

 severely affected tissue in mammals. The action is in most case biphasic. 

 There is usually an initial stimulation, manifested by restlessness, increased 

 reflex excitability, muscle twitchings, ataxia, and either clonic or tonic 

 convulsions; this may be followed by a period of depression characterized 

 by paralysis, loss of reflex activity, respiratory depression, coma, and death. 

 Other results of central stimulation probably are salivation, emesis, and 

 the early respiratory irregularities and the fluctuations in blood pressure. 

 Effects on the circulation are often not marked but there is usually a fall 

 of the blood pressure early in the poisoning and evidences of vasodilatation. 

 The direct effect on the heart is a slowing but initially this may be ob- 

 scured by a central sympathetic discharge. Occasionally there are cardiac 

 dysrhythmias and terminally the heart is always weak. Since isolated skeletal 

 muscle is reasonably sensitive to the quinones, it is interesting to consider 

 how much of the motor disturbance is central and how much peripheral. 

 The nature of the response in most cases clearly indicates a central origin 

 and in frogs, at least, this has been experimentally demonstrated, since the 

 convulsions still occur following ligation of the vessels to a leg but disap- 

 pear after severing the nerve. However, it is possible that peripheral effects 



