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
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.