Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.344367
Title: The neuropharmacology of some injectable anaesthetics studied in the lamprey
Author: Cullen, K. D.
ISNI:       0000 0001 3400 0234
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1983
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Abstract:
A comparative study of four anaesthetic drugs has been undertaken with the object of improving the understanding of their neuropharmacology. Pentobarbitone, ketamine (Vetalar*), alphaxalone (Saffan*) and metomidate have been selected to represent the types of compound currently in clinical use. With a more extensive knowledge of the drugs at their disposal clinicians will be better able to exploit the different properties of individual drugs. Intracellular recordings have been made from identified bulbar reticulo-spinal (M'uller) cells in the medulla of lamprey ammocoetes. Responses to iontophoretically applied transmitters have been measured as changes in membrane potential and input resistance. Bath application of anaesthetics resulted in dosedependent alterations in the responses to α-aminobutyric acid (GABA), glycine and glutamate. These amino acids are transmitters thought to be of major importance in central nervous mechanisms. The suitability of the lamprey preparation for a pharmacological study of this nature is discussed. All four drugs have been tested and shown to anaesthetise lampreys; although pentobarbitone was effective only when administered by injection. Anaesthetic effects on the spontaneous synaptic activity recorded from Müller cells have been measured: EPSPs were decreased in frequency by pentobarbitone (10⁻⁴M) and, after a transitory increase, by alphaxalone (1-3 x 10⁻⁵M). Sub-anaesthetic concentrations of ketamine (< 10⁻⁵M) stimulated activity in the one preparation tested. High concentrations (10⁻³M) of all drugs suppressed all spontaneous activity: below this concentration metomidate had little effect. IPSPs were more labile than EPSPs: they were reduced in frequency by all drugs at anaesthetic or supraanaesthetic concentrations, and this reduction was longer lasting than that of EPSPs GABA responses were potentiated by pentobarbitone (1-3 x 10⁻⁴M) and prolonged by ketamine (3.7 x 10⁻⁴M); but depressed by high concentrations (10⁻³M) of all drugs, as well as by anaesthetic concentrations of alphaxalone (1-3 x l0⁻⁵M) . Glycine responses were depressed by alphaxalone (1-3 x l0⁻⁵M) and by supra-anaesthetic concentrations of ketamine (3.7 x 10⁻⁴M) and metomidate (1.8 x 10⁻³M). No drug potentiated the glycine responses. Anaesthetic effects on glutamate responses were more variable and much less striking than were those on GABA and glycine responses. Only pentobarbitone and ketamine had consistent dosedependent inhibitory effects. No potentiation of glutamate responses was observed. In the absence of an effect common to the four anaesthetics, it is concluded that neither potentiation nor inhibition of all GABA, glycine or glutamate responses is an essential feature of anaesthesia. However, effects comparable to those described here may contribute to the overall clinical picture during anaesthesia of higher vertebrates. Attention is drawn to the difficulty of predicting the consequences of effects observed on a single component of a polysynaptic pathway. The findings do not support the notion that all anaesthetic agents act on biological membranes by a single mechanism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.344367  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry
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