Monoamine neurotransmitter

About: Monoamine neurotransmitter is a research topic. Over the lifetime, 7577 publications have been published within this topic receiving 295853 citations. The topic is also known as: monoamine neurotransmitter.

p-CHLOROPHENYLALANINE: A SPECIFIC DEPLETOR OF BRAIN SEROTONIN

Abstract: p -Chlorophenylalanine has been found to be a potent and selective depletor of brain serotonin (5HT) in mice, rats and dogs. Brain 5-hydroxy-3-indolylacetic acid (5HIAA) content was also depleted by the drug, but catecholamine concentrations were only slightly decreased. Peripheral stores of 5HT were also lowered. In rats, p -chlorophenylalanine reduced the normal increase in brain 5-hydroxyl-3-indolyl compounds following L-tryptophan loading (without apparently affecting tryptophan uptake into brain), completely prevented the increase in brain 5HT accompanying inhibition of monoamine oxidase by pargyline and blocked the increase in brain 5HIAA usually observed after reserpine treatment. p -Chlorophenylalanine slightly diminished the usual increase in brain 5HT in rats following 5-hydroxytryptophan (5HTP) administration, but decreased the rate of disappearance of excess 5HT and antagonized the increase in brain 5HIAA. p -Chlorophenylalanine did not inhibit monoamine oxidase or 5HTP-decarboxylase in vitro and exerted no effect on monoamine oxidase or 5HTP decarboxylase activity of rat tissues in vivo. In contrast, p -chlorophenylalanine inhibited liver tryptophan hydroxylase in vitro and strongly suppressed the tryptophan- and phenylalanine-hydroxylating capabilities of livers of rats treated with it. These results suggest that p -chlorophenylalanine may effect 5HT depletion by inhibiting the biosynthesis of this monoamine, possibly by blocking tryptophan hydroxylation. A blockade of uptake of amino acid precursor might also contribute to the effect of decreasing 5HT biosynthesis. The slow depletion (2-3 days) of brain 5HT induced by p -chlorophenylalanine suggests that an active metabolite might be formed. p -Chlorophenylpyruvic acid exerted essentially the same pharmacologic effects as the amino acid, but it cannot be ascertained at present whether it is the active metabolite because of the interconversion of α-amino acids and α-keto acids in vivo. p -Chlorophenethylamine may be excluded as the metabolite responsible for the action of p -chlorophenylalanine because of the brief duration of the amine in brain and the short lasting, nonselective decrease of both 5HT and norepinephrine produced by the amine. A study of structural variation in the phenylalanine series indicated a specific requirement of a single chlorine substituent in the para position for potent in vivo activity. Rats treated with p -chlorophenylalanine displayed few apparent signs, and certainly not sedation. p -Chlorophenylalanine did not block characteristic signs elicited by reserpine or tetrabenazine in rats. Accordingly, the central actions of reserpine and reserpine-like drugs may possibly be dissociated from both 5HT concentrations and the formation of new 5HT in brain.

Evidence for the existence of monoamine neurons in the central nervous system. 3. the monoamine nerve terminal.

Abstract: With the help of the highly specific and sensitive fluorescence method of Falck and Hillarp together with the histochemical and pharmacological criteria for the specificity of the fluorescence reaction convincing evidence has been obtained that the fine, varicose nerve fibres observed in a vast number of regions in the mammalian central nervous system (mouse, hamster, rat, guineapig, rabbit, cat), which exhibit a green or yellow fluorescence, contain primary catecholamines and 5-HT respectively. Strong support has been given for the view that CA fibres showing a rapid recovery after administration of α-MMT contain DA, while those showing a slow recovery contain NA. There is little doubt that the monoamine-containing fibres in the brain represent the terminal ramifications of axons belonging to specific monoamine neurons and that they are true synaptic terminals. They seem to make their contacts via the varicosities which have extremely high concentrations of amines and in all probability represent the presynaptic structures, specialized for synthesis, storage and release of the amines. The central monoamine terminals thus have the same characteristic appearance as the adrenergic synaptic terminals in the peripheral nervous system. All the data strongly support the view that the specific central neurons giving rise to the terminals are monoaminergic, i.e. function by releasing their amines from the synaptic terminals. Consequently, DA, NA and 5-HT seem to be central neurotransmitters. Not only the median eminence but also the nuc. caudatus putamen, tuberculum olfactorium, nuc. accumbens and the small circumscribed areas medial to nuc. accumbens contain very fine (partly sublightmicroscopical) CA terminals. These areas react to treatment with reserpine, nialamide-dopa and α-MMT in the same way and since the nuc. caudatus putamen and tuberculum olfactorium are known to have a high DA content it seems likely that abundant DA terminals are accumulated in these special areas.