Pharmacology 183 



up to 5 nig. colchicine, the hcnion hagcs arc apjiarcni after 8 hours. 

 This docs not appear lo be in any wax rehited to a release ol his- 

 tamine.'* which is one ol the toxic actions ol colchicine locally ajjplicd 

 on the skin.'"' 



Recent work-'' indicates that colcliicine has no direct action on 

 the smooth muscle ol tlie intestine. 



-.5-7; Hfuirl iind ciniilatioti. The heart is apparently in- 

 sensitive to colchicine, either in irogs or in manunals. The isolated 

 heart ol the frog may beat in a 1 per cent solution ol colchicine.-" 

 in mammals, the heart may go on contracting regularly for as long as 

 two hours after death by colchicine poisoning."^ As a consecpience, 

 blood pressine is onh depressed immediately before death. 



There is no "cneral agreement about action on xasomotor nerves. 



1 1 - ■ 



A\'hile having no action on the heart's sympathetic fibers, •''= colchicnie 

 has been found to increase the hypertensive action of epinephrine 

 in the rabbit under urethane anesthesia. i- In a dog under chloralose 

 anesthesia, a similar potentiating effect could be measuied 1)\ changes 

 in blood pressure and intestinal contraction.-^*^ This latter observation 

 has not been confirmed, and only the excitatory actions of ej)inephrine 

 on the \ascidar bed aj)ijear to be well pro\ed.-'' 



7.4: Disturbances Possibly Related to Mitotic Poisoning 



Several remarkable effects of the alkaloid will be gathered under 

 this heading. Our purpose is, when possible, to relate pharmacological 

 effects to the histological changes resulting from spindle destruction. 

 However, this is ob\ iously far from being simple, and this paragraph 

 should only be considered as a tentative grouping of cellular reactions. 

 It will i)e noticed that the leukocytosis-promoting effect of colchicine, 

 which nearh led to tlie discovery of its action on mitosis,-"- -^ is 

 probablv only remotely linked to mitotic arrest. Its origin may be the 

 action of the drug on the central ner\ ous system. Howe\er, it is associ- 

 ated with some of the first descriptions of tissues altered by colchicine, 

 and has often been tjuoled as the origin of modern cytological work 

 in this field. For this reason, the problem will receive more attention 

 here. 



j.^-i: A(ti())i on the blood. A substance that arrests h)r some 

 hours the mitoses taking place in the bone marrow and destro\s many 

 of them, would be expected to dej^ress blood lormation. Kxiensive 

 celhdar destruction has been lound in the bone marrow ol nmc.'" 

 Considerable congestion and a decrease in the number of nucleated 

 cells are the consequence of this destruction, in some expeiiments. 20 



Fig. 7.3 — Action of colchicine on the isolated Sartorius muscle of the frog. Broken 

 lines: controls. The oxidative activity and anaerobic glycolysis are measured on cof- 

 feinafed muscle (1.9 x 10 'M). The lactate concentration is expressed in microgm gm 

 of muscle. (After Ferguson,"^ slightly modified) 



