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9 - Drug interactions with inhibitory amino acids

from CENTRAL NERVOUS SYSTEM

Published online by Cambridge University Press:  08 October 2009

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Summary

A number of drugs interact with the inhibitory neurotransmitters glycine and γ-aminobutyric acid (GABA) either as competitive receptor antagonists (strychnine and bicuculline), as non-specific channel blockers (picrotoxin), to reduce their release from terminals (tetanus toxin) or by more complex interactions with the receptors leading to a potentiation of the effect of the transmitter (benzodiazepines, some barbiturates and some anti-epileptic drugs). The functions of glycine and GABA as inhibitory transmitters and the actions of antagonists are discussed in Chapter 5. Fig. 9.1 summarises drug interactions with inhibitory amino acids and their receptors.

The pharmacological and clinical implications of drugs which modulate the effect of the inhibitory amino acids, either to reduce or to enhance their effects, are numerous and are subdivided in this chapter into three groups (convulsants, anxiety-reducing drugs and anti-epileptic drugs): some drugs, e.g. benzodiazepines and barbiturates, are both anxiety-reducing and anti-epileptic. The boundary between these is therefore indistinct. The barbiturates are considered in more detail in Chapter 7, principally as anaesthetic agents. It should be remembered that not all of the actions of anxiety-reducing and anti-epileptic drugs can be explained simply in terms of their interactions with the inhibitory transmitters, and there may be additional factors involved in determining which drug or group of drugs is more effective in particular clinical states.

Convulsants

Strychnine, bicuculline, picrotoxin and tetanus toxin all reduce the effectiveness of amino acid-mediated inhibitory neurotransmission but they do so in different ways. Strychnine and bicuculline are competitive antagonists at the glycine and GABA-A receptors, respectively (see Chapter 5). Picrotoxin blocks the chloride channels which are opened by both amino acids.

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Publisher: Cambridge University Press
Print publication year: 1989

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