Study of analeptics

Abstract

The improvement of lowered conditions of vitality brought on by disease or poisoning must have been a problem engaging the serious attention of people practising the healing art from the earliest days of human civilisation. This led to the use of various agencies, supposed to possess reviving powers, some of which survived through long periods of usage. Therapeutics in early days was purely empirical. Even after considerable advances in the knowledge of the pathology of these lowered conditions of vitality, very little attention was paid to enquiring into the nature of the reviving power of these agencies(by which was perhaps meant the improvement of some symptoms of lowered conditions). In many cases the improvement was due to the strong local irritant action of alcohol and other irritant constituents of the medicaments on the gastric mucosa, setting up a strong reflex stimulation of the respiratory and vasomotor centres and also perhaps partly to alcoholic contents thereof, acting as a diffusible stimulant, and supplying ready nutrition to tissues. A few did act after absorption, and some of these caused improvements in lowered conditions by improving the circulation as cardio -vascular stimulants and a few others really acted through the nervous system, especially through the respiratory and other vital centres.Development of modern surgery brought in its train the use of anaesthetics which have their risks of extreme depression. This inspired an increased study of the nature of reviving drugs. With the rapid increase in the use of barbiturates as basal narcotics and anaesthetics, and also with the occurrence of poisoning, following their therapeutic administration, self- medication or suicidal attempts, the study of analeptic drugs has, in recent years, been engaging a good deal of attention of pharmacologists. Of the older drugs, picrotoxin and strychnine have been very thoroughly investigated, as also coramine and cardiazol amongst the newer synthetic drugs. Caffeine, cocaine, ephedrine, lobeline and a few others have also received some attention.The clinical use of some of these still persists in spite of their questionable status as judged by experimental evidences.No doubt a good number of therapeutic agents are of more or less symptomatic value in combating some of the effects of hypnotics and narcotics. But there is still a good deal of lack of unanimity regarding their usefulness in different stages of depression produced by the narcotics. The importance of the subject therefore called for further study of the analeptics.Moreover, methods employed for the study of the problem were diverse in nature, and most of them had some unsatisfactory feature or other. For a truer evaluation and determination of the comparative worth of these drugs it was found necessary to evolve an efficient method free from those unsatisfactory features. Investigations undertaken for these purposes form the subject of this thesis.Appendix - Two reprints from Quart. J. exper.Physiol. (a) Antagonism of evipan by picrotoxin, coramine and cardiazol. 1939 . 29, 355. || (b) (with J. Raventos). The Clearance of sodium evipan. 1939. 29, 343.