450 YOUNGKEN, JR. 



have been noted as far as decreasing blood pressure and heart rate. The action 

 of khelHn as a smooth muscle relaxant has led to its use in bronchial asthma 

 with some success. It is rapidly and efficiently absorbed and found to be 

 widely distributed in the body. Side effects from khellin medication have 

 been chiefly those of nausea, mental depression, and some insomnia. But its 

 margin of safety has been considered to be rather wide. 



All these hypotensive agents have more persistent activity than the nitrites 

 and nitrates, but in general their onset of action is not as prompt. The locus 

 for Veratrum and Rauwolfia activity appears to be in the cerebrum and 

 hypothalamus, that is, much higher up in the central nervous system than 

 other hypotensive agents such as the tetraethyl ammonium and hexametho- 

 nium drugs. The nitrites, on the other hand, act essentially on the muscula- 

 ture of the end organs without nerve innervation. When combined with the 

 latter drugs the virtues of Veratrum and Rauwolfia as hypotensive agents are 

 often more useful. It is for this reason that a large variety of mixtures which 

 include several types of each botanical constituent and organic nitrate or 

 hydralazine compound (Apresoline) are employed. The search for hypotensive 

 agents among other plants has continued at a rapid rate in many laboratories, 

 and it is likely that newer hypotensive compounds from still other "old" 

 botanicals will turn up. 



Muscle relaxants and antispasmodics. A number of botanicals have in the 

 past been employed for sedative effects in intestinal and stomach cramps and 

 essential or functional dysmenorrhea. Research in the pharmaceutical industry 

 has frequently pursued the search and synthesis of new and better antispas- 

 modics. Atropine and atropine-like synthetics certainly lead the field of anti- 

 spasmodics today. But side effects from most of these still limit their applica- 

 tions. It is largely for this reason that the search continues. Plant drugs such 

 as Viburnum, Aletris, Helonia, blessed thistle, Jamaica dogwood (Piscidia 

 spp.), and Potentilla (silverweed) are examples of a few botanicals that have 

 entered into pharmaceutical formulations for antispasmodic purposes. These 

 are plants which are indigenous to areas of the United States, and Jamaica 

 dogwood particularly to the West Indies. The activity of some of the crude 

 extract materials of the above plants has been supported in a rather hap- 

 hazard way by clinical data, but because of the composite nature of their 

 mixtures and since significant active chemical components have not yet been 

 isolated from them, it has been difficult to properly evaluate them. Many 

 factors are involved in the formation of plant constituents, for example, the 

 influence of growing seasons, soil conditions, and methods of harvest and 

 drying. These factors are often reflected in the decrease or increase of activity 

 that can be shown when extracts of such plants are tested pharmacologically. 

 Until more knowledge is achieved relative to the effects of such factors on the 

 formation of active principles of the above plants, it is very difficult to know 

 when to collect materials which will have the most potent activity. 



