7 Local Anaesthetics

Wiedling, Sten; Tegnér, Claës

doi:10.1016/s0079-6468(08)70121-8

Cited by 16 publications

(3 citation statements)

References 204 publications

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“…Thiamine and other substances.-A variety of other naturally occurring substances have been claimed to modify, usually antagonistically, the action of local anesthetics [see (108) ]. These include certain water-soluble vita mins, particularly thiamine; ·the amino acids, aspartic acid, tryptophan, leu cine, and cysteine'; the veratrum alkaloids ; and urea.…”

Section: Biochemical Aspects Of Local Anesthetic Actionmentioning

confidence: 99%

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On the Mode of Action of Local Anesthetics

Ritchie¹,

Greengard²

1966

Annu. Rev. Pharmacol.

236

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Local anesthetics possess the specific ability to bl ock conduction in nerve in a reversible ma nner and in low concentration. The reactions that occur in the ner ve membrane that allow local anesthetics to achieve this effect are still not clearly defi ned. Howe ver , with the re cent increa se in our knowledge of the nature of the nerve impul se , some idea of the mode of action of local anesthetics is be ginning to form. Measurements of me m brane potentials and ionic move me nt s have strong ly suggested that local anesthetics block cond uct ion by inter fe ring with the sodium and potassium conductance cha ng es that are fundamental to the generation of the nerve impulse . Other studies have indicated that local anesthetic molecule s achieve this conduction block in the form of ca ti ons. Furthermore, studies of structure-activity relations have suggeste d someth ing of the chemical na ture of the re ce ptor in the nerve membrane and the method of interac tion of this receptor with the local anesthetic molecule . Finally, studies of the be ha vior of loca l anesthetics in model systems have suggested a phys icochemical ba sis for the mode of action of local anesthetics on the ne rve membrane. These various aspects of local anesthetic action will be g iven particular emphasis in this review. Many other, perhaps equally important, aspects will be neglected, and the interested reader is there fore referred to the many comprehensive reviews on local anesthetics that have appeared in the last decade (4,14,24,25,56,73,94,104,106,108). ELECTROPHYSIOLOGICAL EFFECTS OF LOCAL ANESTHETICSThe work of Hodgkin, Huxley, Keynes, and ot hers [see (52)] has led in recent year s to a better under standing of the nature of the nerve im pulse . In consequence , it is now possible to expla in the action of local an esthet ics within the fra me wor k of the ionic theory of nervous act ivity .Active nerve membrane.-Local anesthetics increase the threshold for ele ctr ical excitat ion in nerve , slow pr opagation of the impul se, reduce the rate of rise of the action pote nt ial, and eventually bl ock conduct ion [e.g. (85)]. They do this by inter fer ing with the pr oce ss fundamental to the gen eration of the nerve action pote ntial, name ly the large transient rise in the permeability of the me mbrane to sodium ions that is produced by a slight de pola rization of the me mbrane. Taylor (99), Shanes et al. (85), and, more re ce ntly, Blaustein & Goldman (19) used the voltage-clamp me thod to study 1 The survey of th e literature pertaining to this review was concluded in Octo ber 1965. 405 Annu. Rev. Pharmacol. 1966.6:405-430. Downloaded from www.annualreviews.org Access provided by Queens University -Kingston (Canada) on 03/08/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS

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Section: Biochemical Aspects Of Local Anesthetic Actionmentioning

confidence: 99%

“…These various aspects of local anesthetic action will be g iven particular emphasis in this review. Many other, perhaps equally important, aspects will be neglected, and the interested reader is there fore referred to the many comprehensive reviews on local anesthetics that have appeared in the last decade (4,14,24,25,56,73,94,104,106,108). …”

mentioning

confidence: 99%

On the Mode of Action of Local Anesthetics

Ritchie¹,

Greengard²

1966

Annu. Rev. Pharmacol.

236

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“…It seems therefore that acetylcholine stimulated muscarinic receptors sited on the smooth muscle fibres. Procaine displaced the dose-response curve to acetylcholine slightly to the right, an action which is best explained by its known anti-acetylcholine property (Sinha, 1953 ;Wiedling & Tegner, 1963).…”

Section: Discussionmentioning

confidence: 99%

An analysis of the action of drugs on the circular muscle strips from the caecum of the guinea-pig

Akubue

1966

Journal of Pharmacy and Pharmacology

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The taenia-free circular muscle strips of the caecum of the guinea-pig contracted t o acetylcholine or histamine. 5-Hydroxytryptamine produced small contractile responses but high concentrations (40 pg/ml or more) induced relaxation. The contractions to 5-hydroxytryptamine were enhanced by the organophosphorus anticholinesterase drug mipafox. The responses to nicotine were always relaxations but contractions were obtained after incubating the preparation with mipafox. Hence circular muscle strips treated with mipafox were used to investigate the mechanism of contractions to all the drugs. The site of action of acetylcholine or histamine was located on the smooth muscle cells because the responses were not blocked by pentolinium, dimethylphenylpiperazinium, procaine or cocaine. Hyoscine blocked the responses to acetylcholine but left those to histamine unchanged. The contractions to nicotine were blocked by hyoscine, local anaesthetics or ganglion blocking drugs.5-Hydroxytryptamine produced contractions which were potentiated by mipafox, blocked by hyoscine and almost abolished by local anaesthetics. The responses were not modified by pentolinium but were reduced by dimethylphenylpiperazinium at a concentration which did not block the responses to acetylcholine or histamine. It is concluded that the action of 5-hydroxytryptamine was wholly indirect, on nervous tissues, part of which was located on cholinergic ganglion cells.Nicotine is thought to activate cholinergic ganglion cells.

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