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Martin WR, Vaupel DB, Sloan JW, Bell DA, Nozaki M, Bright LD.
“The Mode Of Action Of LSD-like Hallucinogens And Their Identification”.
Psychopharmacology of Hallucinogens. 1976;p118-125.
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Abstract
This paper will describe a series of experiments that have been done to demonstrate that tryptamine is a neurotransmitter in the brain and that one of the primary modes of action of the LSD-like hallucinogens is their ability to function as tryptaminergic agonists. The second purpose of this paper will be to show how some of the methods developed in demonstrating that LSD and similar hallucinogens are tryptaminergic agonists have been applied in the identification of the mode olfaction of substituted amphetamines. Our interest in the LSD-like hallucinogens was stimulated by observations that in the chronic spinal dog LSD facilitated the hindlimb flexor reflex and evoked the stepping reflex, dilated pupils, increased respiratory and pulse rate, and elevated body temperature, a syndrome not unlike that seen in man with LSD-like hallucinogens, and that these effects were also produced by psilocin, mescaline and-DOM. It was further observed that tryptamine produced a similar constellation of signs in the chronic spinal dog (Martin and Lades, 1970). It was also shown that the effects of LSD, mescaline, psilocin, DOM and tryptamine were selectively antagonized by cyproheptadine but not by phenoxybenzamine. Studies by Vaupel and Martin (1976) demonstrated that tryptamine facilitated the mono- and polysynaptic segmental reflexes of the acute spinal cat and this facilitatory action was antagonized by cyproheptadine but not by phenoxybenzamine. Isbell et al, (1956) used the facilitation of the patellar reflex in man as one of the indicators of LSD-like activity and showed that tolerance and cross tolerance developed to this effect. These data, as well as other data, strongly suggested that the LSD like hallucinogens were mimicking the actions of tryptamine and that the actions of tryptamine did not involve noradrenergic processes. It was not until the series of experiments undertaken by Bell and Martin (1974) in which the effects of LSD and tryptamine were studied on the C-fiber reflex of the acute spinal cat that it was shown that the LSD-like hallucinogens were operating through a tryptaminergic and not a serotonergic mechanism. Bell and Martin (1974) first showed that LSD facilitated the C-fiber reflex as did tryptamine, and this facilitatory action was selectively antagonized by cyproheptadine. Bell et of. (1976) further showed that l-tryptophan facilitated the flexor reflex in the acute spinal cat and that the facilitatory effect was antagonized by cyproheptadine and alpha methyldopa which inhibits the decarboxylation of l-tryptophan to tryptamine but not by p-chlorophenylalanine which inhibited the conversion of t-tryptophan to 5-hydroxytryptophan.
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