Some Aspects of Central Nervous Pharmacology

Toman, James E. P.

doi:10.1146/annurev.pa.03.040163.001101

Cited by 29 publications

(8 citation statements)

References 35 publications

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“…The peculiar " rage-like " effect seen in cats after the injection of tremorine or its metabolite, oxotremorine (Toman, 1963), prompted a study of the effects of oxotremorine. The drug was given in two doses (0.25 and 0.125 mg/kg, intravenously) spaced at an interval of 2 hr in cats protected from the peripheral effects of the drug by an injection of atropine methylbromide (1.5 mg/kg, subcutaneously) 15 min before the first injection.…”

Section: Excitant Drugsmentioning

confidence: 99%

Modification by Drugs of the Metabolism of 3,4‐dihydroxyphenylethylamine, Noradrenaline and 5‐hydroxytryptamine in the Brain

Laverty

Sharman

1965

British Journal of Pharmacology and Chemotherapy

149

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There have been a number of studies of the effects of drugs on the content of various amines found in brain tissue. In particular, the concentrations in the brain of noradrenaline (Vogt, 1954) and 5-hydroxytryptamine (Paasonen & Vogt, 1956;Brodie, Shore & Pletscher, 1956) have been determined before and after treatment with drugs, and many attempts have been made to correlate the change in brain amine concentration with an observable change in animal behaviour. Later, brain dopamine (3,4-dihydroxyphenylethylamine) has been included in such studies (Bertler, 1961).In the present experiments, the content of dopamine, noradrenaline and 5-hydroxytryptamine in different parts of cat and dog brain was measured, and so was the content of homovanillic acid (4-hydroxy-3-methoxyphenylacetic acid) and 5-hydroxyindol-3-ylacetic acid, the major acid metabolites of dopamine and 5-hydroxytryptamine. The corresponding acid metabolite of noradrenaline, vanillylmandelic acid (4-hydroxy-3-methoxymandelic acid), has not been detected in brain tissue (Anden, Roos & Werdinius, 1964; Sharman, unpublished) and so could not be determined. The simultaneous determination of an amine and its metabolite permitted a study of the effect of the drug not only on the content of the amine but also on a possible indicator of the rate of metabolism of the amine.The concentrations of both dopamine and homovanillic acid are highest in the brain in the caudate nucleus and putamen; since the caudate nucleus is easy to dissect out reproducibly it was used for the estimation of these two compounds. The caudate nucleus is thought to form part, with other basal ganglia which also contain dopamine, of the " extrapyramidal motor system", though recent evidence suggests that it has a more generalized function, acting as an integrative centre for the whole of the cortex (Laursen, 1963;Carman, Cowan & Powell, 1963 (Laverty, 1963;Sharman, 1963b (1958). The column was fitted with a capillary tube which maintained a flow rate of 8 to 10 ml./hr without applied pressure. When the supernatant fluid had run through, the column was washed with 4 ml. of water; then the noradrenaline was eluted with 8 ml. of 0.4 N-hydrochloric acid. A further fraction which contained dopamine could be obtained by eluting with 8 ml. of 2 N-hydrochloric acid. The columns used for caudate nucleus extracts were washed with 6 ml. of 0.4 N-hydrochloric acid instead of water to remove any noradrenaline or dihydroxyphenylalanine, and the dopamine was eluted with 8 ml. of 2 N-hydrochloric acid.Edetic acid disodium salt (20,.tg) was added to the dopamine eluates which were then brought to pH 4 with solid sodium bicarbonate.Noradrenaline in the eluates was determined fluorimetrically by a ferricyanide oxidation method (Sharman, Vanov & Vogt, 1962). The fluorescence was measured using a Locarte filter fluorimeter with a Chance OX1 primary filter, and an Ilford 625 secondary filter. This filter combination gave equivalent fluorescence with equal amounts of noradrenaline and adrenaline; the result...

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Section: Excitant Drugsmentioning

confidence: 99%

Modification by Drugs of the Metabolism of 3,4‐dihydroxyphenylethylamine, Noradrenaline and 5‐hydroxytryptamine in the Brain

Laverty

Sharman

1965

British Journal of Pharmacology and Chemotherapy

149

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“…Toman (194) has summarized the attempt of the present reviewer to interpret the actions of drugs in terms of their effects on electrogenic mechan isms (77,81,85). A brief restatement of these views will be included partly because Toman's version was wrong in a few respects and partly to stress at this time that effects on non synaptic electrogenic membrane must be in cluded in the analysis of drug action.…”

Section: Theories In Neuropharmacologymentioning

confidence: 99%

“…N a activa- (136) to employ the term "chemical synapses." However, in most cases of well studied synaptic systems, the direct evidence that the transmission is mediated by chemical agents is simply absent (85,92,193,194). Indeed, the role of acetylcholine in various cholinergic systems is still unsettled (114).…”

Section: Theories In Neuropharmacologymentioning

confidence: 99%

Effects of Drugs on the Central Nervous System

Grundfest¹

1964

Annu. Rev. Pharmacol.

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The editors instructed me to be "fiercely selective" in the material that I was to include in this chapter. In one respect that is an easily followed in struction for a general physiologist who studies cell membranes and attempts to use pharmacology as a tool to help decipher the electrogenic phenomena of excitable cells. Electrophysiology is fortunate in having a theory which links electrogenesis with the permeability of the cell membrane to ions (25, 100). The dazzlingly quantitative application of this theory to account for the spike of the squid axon (101) is meeting with the stubborn complexities of living membranes (13,14,95,144,188,189). Nevertheless, some rela tively simple modifications of the ionic theory permit the latter to account, although only qualitatively at present, for the bulk of a large variety of electrophysiological and pharmacological phenomena (84,85,89,90).The situation appears to be quite different in pharmacology. The periodi cal literature seems to be styled after the biblical "begat" chapters and much of it is about equally innocent of theory. Even in the restricted field of neuro pharmacology the data are almost entirely based on various reactions of whole animals or of their individual organ systems. When theory is attempted it seems to regard as irrelevant the morphology and functional properties of individual neurons and effectors, and of their organization into the complex organ system of the neuraxis and its peripheral appendages.In another respect, however, this instruction must be disobeyed. The present reviewer arrived at his interest in neuropharmacology from an at tempt to use a relatively simple conceptual framework, gained from the study of peripheral junctions (78 to 80), to account for the actions of drugs on cells, including those of the central nervous system (77, 81). The studies on electrocortical phenomenon with Purpura and other colleagues (82, 148, 151, 152, 154 to 156) in which pharmacological tools were used extensively 1 The survey of the literature pertaining to this teview was concluded in July 1963.

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“…Although there are several rigorous criteria for identification of a substance as a synaptic transmitter (Rosenblueth, 1950;Crossland, 1957;Paton, 1958;Florey, 1960;Toman, 1963), pharmacological confirmation of a 'receptor' to the substance on the post-synaptic membrane and evidence for its liberation from presynaptic terminals can be considered as two minimal requirements (Terzuolo & Edwards, 1962; Grundfest, 1964). While the former criterion for cholinergic synapses on Renshaw cells has for the most part been fulfilled (see above), no systematic approach has been made toward evaluating the latter criterion.…”

Section: Introductionmentioning

confidence: 99%

The release of acetylcholine from the spinal cord of the cat by antidromic stimulation of motor nerves

Kuno¹,

Rudomín²

1966

The Journal of Physiology

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SUMMARY1. ACh was measured in the effluent from the perfused lumbosacral cord of the cat with or without stimulation of the central ends of the cut left sciatic and femoral nerves after section of the left dorsal roots.2. In about 30 % of the preparations ACh was obtained in the samples collected at rest (average 3'3 ng/min); the amount of ACh release was increased 1-3-9 times by stimulation of the peripheral nerves. The average amount of ACh collected during stimulation of the peripheral nerves at 5/sec was 6-9 ng/min. Antidromic motor nerve impulses responsible for the ACh release were likely to be only those in alpha motor fibres.3. There was a depression in ACh release/stimulus as the stimulus frequency was increased more than 10/sec. Such changes in ACh release with various stimulus frequencies were correlated with depression in the response of Renshaw cells to excitation through motor-axon collaterals.4. Amounts of ACh release during stimulation of the peripheral nerves at 5/sec were significantly increased for 1 or 2 min after a short tetanic stimulation of the nerves.5. Intravenous injection of dihydro-fl-erythroidine did not reduce the amount of ACh release produced by stimulation of the peripheral nerves.6. It is concluded that antidromic impulses in alpha motor fibres liberate ACh from the presynaptic terminals at the central synapses on Renshaw cells.

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Some Aspects of Central Nervous Pharmacology

Cited by 29 publications

References 35 publications

Modification by Drugs of the Metabolism of 3,4‐dihydroxyphenylethylamine, Noradrenaline and 5‐hydroxytryptamine in the Brain

Modification by Drugs of the Metabolism of 3,4‐dihydroxyphenylethylamine, Noradrenaline and 5‐hydroxytryptamine in the Brain

Effects of Drugs on the Central Nervous System

The release of acetylcholine from the spinal cord of the cat by antidromic stimulation of motor nerves

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