Actions of Certain Amines on Cerebral Cortical Neurones

Krnjević, K.; Phillis, John W.

doi:10.1111/j.1476-5381.1963.tb01484.x

Cited by 202 publications

(58 citation statements)

References 42 publications

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“…The ability of LSD to antagonize two excitant transmitters on the 5-HT sensitive neurones may contribute to its much higher psychotomimetic potency than those of the tryptamine derivatives. LSD rarely, if ever, antagonizes specifically the inhibitory effects of 5-HT, whether it is iontophoretically applied (Krnjevic & Phillis, 1963;Bloom, Costa & Salmoiraghi, 1964;Legge, Randic & Straughan, 1966;Roberts & Straughan, 1967;Boakes et al, 1970) or released from presumed serotoninergic synapses .…”

Section: Discussionmentioning

confidence: 99%

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

Bradley

Briggs

1974

British J Pharmacology

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1The actions of 5-methoxytryptamine (5-MeOT), N,N-dimethyltryptamine (DMT), 5-hydroxy-N,N-dimethyltryptamine (bufotenine, 5-HODMT) and 5-methoxy-N,Ndimethyltryptamine (5-MeODMT), and their interactions with 5-hydroxytryptamine (5-HT), acetylcholine, (-)-noradrenaline, and glutamate were studied by microiontophoresis on single neurones in the brain stem of rats anaesthetized with urethane or decerebrate cats. 2 Like D-lysergic acid diethylamide (LSD 25) the three psychotomimetic derivatives (DMT, 5-HODMT, 5-MeODMT) specifically antagonized 5-HT excitations of single neurones, but the non-psychotomimetic 5-MeOT had no antagonistic effects. 3 In contrast to LSD 25, the psychotomimetic tryptamines only rarely antagonized glutamate effects, indicating that the excitatory 5-HT receptors and the glutamate receptors on the same neurones may be closely related spatially, but are separate. 4 The methylated tryptamine derivatives were able to mimic the actions of 5-HT on neurones. The non-psychotomimetic 5-MeOT was most potent in this respect, while the other three derivatives which are psychotomimetic, were less active. 5 The 5-HT mimicking actions of 5-MeOT were the same in rats pretreated with p-chlorophenylalanine or reserpine as in untreated rats. It therefore seems that the 5-HT mimicking actions are unlikely to be due to release of 5-HT, but are due to direct actions on 5-HT receptors. 6 The evidence presented supports the hypothesis that LSD-like psychotomimetics act by an antagonism of 5-HT in the lower brain stem, and is not compatible with the suggestion that the psychotomimetic action of these drugs is related to 5-HT receptor stimulation.

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Section: Discussionmentioning

confidence: 99%

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

Bradley

Briggs

1974

British J Pharmacology

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“…The failure of Krnjevic & Phillis (1961, 1963a to demonstrate a depressant action of electrophoretically administered taurine and of 3-amino-i-propanesulphonic acid is rather surprising since, like GABA, each of these sulphonic amino acids readily depresses cortical responses when applied topically in solution to the exposed cortical surface ; but see also Purpura, Girado, Smith, Callan & Grunfest, 1959). Furthermore, when injected intraventricularly into mice, all three amino acids result in a diminution of spontaneous activity, a loss of righting reflexes and eventually a state resembling sleep (Crawford, 1963).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas D-glutamic acid was approximately half to two-thirds as potent as the L-isomer as an excitant of spinal (Curtis & Watkins, 1963) and thalamic neurones (Andersen & Curtis, 1964a), cortical neurones are stated to be very much more sensitive to the L-than to the D-isomer (Krnjevic & Phillis, 1961). Furthermore, N-methyl-D-aspartic acid, a powerful excitant of thalamic, geniculate and spinal neurones (Curtis & Watkins, 1963) has been reported to desensitize cortical neurones to subsequent administration of L-glutamic acid (Krnjevic & Phillis, 1963a), a phenomenon which had not been observed elsewhere in the nervous system in the absence of a depression of nerve cell excitability following excessive depolarization (Curtis & Watkins, unpublished).…”

mentioning

confidence: 94%

“…Furthermore, N-methyl-D-aspartic acid, a powerful excitant of thalamic, geniculate and spinal neurones (Curtis & Watkins, 1963) has been reported to desensitize cortical neurones to subsequent administration of L-glutamic acid (Krnjevic & Phillis, 1963a), a phenomenon which had not been observed elsewhere in the nervous system in the absence of a depression of nerve cell excitability following excessive depolarization (Curtis & Watkins, unpublished). Of the neutral amino acids, Krnjevic & Phillis (1961, 1963a reported that taurine and 3-amino-ipropanesulphonic acid were inactive when ejected near cortical neurones; however, both compounds, particularly the latter, were depressants of spinal interneurones (Curtis & Watkins, 1960b.…”

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confidence: 99%

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The Excitation and Depression of Mammalian Cortical Neurones by Amino Acids

Crawford

Curtis

1964

British Journal of Pharmacology and Chemotherapy

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Amino acids related to L-glutamic and y-amino-n-butyric acid have been administered electrophoretically, and by pressure ejection, into the extraneuronal environment of single neurones in the pericruciate cortex of cats anaesthetized with allobarbitone or allobarbitone-urethane. Acidic amino acids related to glutamic acid, particularly N-methyl-D-aspartic acid, excited cortical neurones. Neutral amino acids related to y-amino-n-butyric acid, particularly 3-amino-1-propanesulphonic acid, depressed cortical neurones. Some of the depressants blocked the antidromic invasion of Betz cells by pyramidal volleys. There are no essential differences between the sensitivities of cortical and spinal neurones towards locally administered amino acids. A transmitter function of such amino acids within the mammalian central nervous system is considered unlikely.When ejected electrophoretically from glass micropipettes, many acidic amino acids related to glutamic acid excite neurones in the feline spinal cord (Curtis,

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“…Histamine and histidine applied iontophoretically both had a weakly inhibitory action on cortical neurones (Krnjevi6 & Phillis, 1963).…”

Section: Discussionmentioning

confidence: 93%

THE EFFECTS OF HISTAMINE AND OTHER NATURALLY OCCURRING IMIDAZOLES ON NEURONES OF HELIX ASPERSA

Kerkut

Walker

Woodruff

1968

British Journal of Pharmacology and Chemotherapy

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There is at present but little evidence to suggest that histamine has the role of a transmitter substance in either the vertebrate or the invertebrate central nervous system. Few studies have, however, been made of the actions of histamine on the central nervous system and those results that have been reported have often been obtained by indirect methods. Furthermore there is still a great deal to be learnt about the nature of the central receptors for histamine.The isolated brain of the snail Helix aspersa is a convenient central nervous system preparation for studying the actions of substances at the cellular level because it contains many large cells, from 80 to 150 [t in diameter, which can be penetrated with microelectrodes. Furthermore, the cells are placed superficially and so allow easy access for drug application. Kerkut & Walker (1962) investigated the actions of a range of chemical substances on single neurones in the snail brain and found that some of the cells responded to histamine. The experiments described in the present paper were undertaken to investigate the possibility that histamine is a transmitter substance in the invertebrate central nervous system and also to obtain information on the broader question of the general nature of histamine receptors in nervous tissue.Some of these results were reported to the meeting of the British Pharmacological Society held at Nottingham in January, 1967. METHODSThe experiments were performed on isolated circumoesophageal ganglionic masses from garden snails, Helix aspersa, which were collected locally. The shell was removed, the animal pinned out and the brain was exposed. The connective tissue covering the brain was removed and the brain was attached to a glass microscope slide with two rubber bands. The whole preparation was immersed in a 20 ml. bath containing snail Ringer solution. The snail Ringer contained (mM): KC1 4; NaCl, 80; CaCl2, 7; MgCl2, 5; Tris HCl, 5. The pH of the Ringer was 8.0.Glass microelectrodes were pulled on a Palmer microelectrode puller and filled with M potassium acetate, or in some experiments, with M potassium chloride. The recording electrodes had a resistance of from 5 to 30 MQ and a tip diameter of less than 0.5 As.

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Actions of Certain Amines on Cerebral Cortical Neurones

Cited by 202 publications

References 42 publications

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

The Excitation and Depression of Mammalian Cortical Neurones by Amino Acids

THE EFFECTS OF HISTAMINE AND OTHER NATURALLY OCCURRING IMIDAZOLES ON NEURONES OF HELIX ASPERSA

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