Capsaicin, a pungent principle present in various species of Capsicum, is a decylenic acid amide [I,R= -(CH2)4CH: CH.CH(CH3)2] of vanillylamine.
CH30 O CH2NH.CO.R HO i JIOn varying the acid portion of the molecule different degrees of pungency of the analogues have been observed (Nelson, 1919; Ott and Zimmermann, 1921;Jones and Pyman, 1925; FordMoore and Philips, 1934). Other pharmacological effects of various species of Capsicum have been reported. Thus Hogyes (1878) first observed that the burning sensation produced by an alcoholic extract of Capsicum annuum dropped upon the skin was accompanied by hyperaemia. Lille and Ramirez (1935) found that intravenous injection of an extract of Capsicum into the dog produced a fall in blood pressure accompanied by a variable effect on the respiration, an increase in salivary secretion and a relatively small increase in gastric secretion. They also observed that capsaicin extracts increased the activity of the isolated rabbit intestine and guinea-pig uterus, although Nast (1923) had previously found that there was a relaxation of the isolated rabbit intestine. Capsaicin also lowers the rectal temperature of the mouse when given subcutaneously (Issekutz, Lichtneckert, and Nagy, 1950)-an effect interpreted as being due to excitation of heat receptors.Heubner (1925) found that undecylenacidic allinyl-amide, an acrid substance related to capsaicin, caused sweating of the forehead of man when smeared upon the mucous membrane of tJe mouth. In a study of gustatory sweating in healthy people Lee (1954) used the fresh fruits of Capsicum frutescens, L., or C. minimum, Roxb. He produced evidence that the reflex was initiated by pain fibres and showed that reflex sweating could not be induced by application of Capsicum to the mucosa of the oesophagus or stomach. He found, however, that Capsicum produced profuse salivation when placed in the mouth. The oleoresin of Capsicum has long been recognized in the B.P. and U.S.P. as a powerful gastro-intestinal stimulant and as a rubefacient.The effects obtained with whole fruits or crude extracts of Capsicum can no doubt be attributed in part to capsaicin. Since some of the effects described could be due to substances other than capsaicin, the pharmacological actions of pure capsaicin and some of its analogues were investigated on animals with particular reference to the circulation and respiration.The compounds studied were capsaicin, vanillyln-decoylamide [I,R = -(CH2)8CH3], vanillyl acetamide [I,R= -CH3] and vanillylamine.
METHODSCats under chloralose anaesthesia were used; the trachea was cannulated and respiration was recorded by measuring the tidal air volume with a closed circuit spirometer filled with oxygen. The blood pressure was recorded either from the femoral or from the carotid artery. Intravenous injections were made direct into the femoral vein, but injections into all other blood vessels were made through cannulae. Injections into the carotid sinus region were made through the lingual artery after clamping the external carot...