Kynuramine: High affinity for [3H]tryptamine binding sites

Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines

“…Nevertheless, serotoninergic actions of 5‐hydroxykynuramine were of interest, because of the structural similarity to the parent indoleamine. In fact, 5‐hydroxykynuramine displayed affinities for the serotonin receptors 5‐HT 1 [130, 136], 5‐HT 2 [130, 146] (5‐HT 2A and 5‐HT 2B [147]), and 5‐HT 3 [146]. In the earlier literature, subtype specificity has not yet been sufficiently clarified, and the pharmacology remains contradictory in certain aspects, especially with regard to 5‐HT 1 receptors (cf.…”

“…It may also exert effects independent of serotonin signaling mechanisms, as the release of prolactin by 5‐hydroxykynuramine was not blunted by melatonin, contrary to the serotonin‐stimulated release [152]; this is in contrast with AMK which did not elicit prolactin secretion [152]. Despite the affinity of 5‐hydroxykynuramine to some serotonin receptor subtypes [130, 136], this has always been less than that of the parent indoleamine. Therefore, the actions observed may be considered as being largely or entirely pharmacological.…”

“…Both kynuramine and 5-hydroxykynuramine stimulated the release of norepinephrine from sympathetic nerve fibers, but only when micromolar levels of these molecules were used [130,137,138]. Conversely, kynuramine also acted as an a 1 -adrenergic receptor antagonist [130,136,139]. As a consequence, kynuramine was capable of either causing a decrease in blood pressure of relatively short duration or an increase explained by a cardiac, indirect sympathomimetic action resulting from norepinephrine release to enhanced heart rate [130].…”

“…The earlier literature was mainly focussed on kynuramine and 5-hydroxykynuramine. Kynuramine was shown to compete with the tryptamine receptor (K i = 28 nm) in the rat frontal cortex [130,136], whereas the 5-hydroxylated, 5-methoxylated and N 1 ,N 1 -dimethylated analogs exhibited much lower affinities to this binding site [130]. Both kynuramine and 5-hydroxykynuramine stimulated the release of norepinephrine from sympathetic nerve fibers, but only when micromolar levels of these molecules were used [130,137,138].…”

[3H]Tryptamine Binding Sites Are Not Identical to Monoamine Oxidase in Rat Brain

“…The discovery of specific binding sites for[ 3H]tryptamine in rat brain significantly strengthened the case for tryptamine as a neurotransmitter (Kellar and Cascio, 1982; Cascio and Kellar, 1983). These sites have been characterized further by several laboratories using both membrane homogenate binding techniques Kellar, 1982, 1986;Bruning and Rommelspacher, 1984;Wood et al, 1984;Charlton et al, 1985;Graham and Langer, 1987) and in vitro receptor autoradiography (Altar et al, 1986;Kaulen et al, 1986;McCormack et al, 1986;Perry, 1986). Abbreviations used: MAO, monoamine oxidase; MAOI, monoamine oxidase inhibitor; MPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine.…”