Seizures Induced

by Convulsant Drugs
Carl L. Faingold

1. lntroduction
From the original insights of Jackson nearly a hundred years
ago (1890) to the recent book by Lockard and Ward (1980), con-
vulsive seizures have been viewed as a window into the function-
ing of the brain, the assumption being that pathophysiology yields
considerable insight into normal physiology. Convulsant drugs
have been a major tool over the years in trying to understand how
and why the brain generates the extensive and dramatic electrical
and behavioral events of generalized seizure. From Oaude Ber-
nard' s pioneering work on the effects of strychnine on the spinal
cord to Jeff Barker's investigations of convulsants in spinal cord
neurons in culture (Barker et al., 1983), these chemical agents have
been used as tools to aid in the understanding of the global events
of epileptic disorders and as molecular probes of subsynaptic
neuronal properties. Since the original discovery that physostig-
mine, the active ingredient in the calibar bean, was capable of pro-
Ionging the actions of a specific neurotransmitter, acetylcholine,
the study of neurochemical actions of drugs with convulsant prop-
erties has developed into a dominant theme in investigations of
the molecular bases of epilepsy. When Curtis and coworkers (1971)
demonstrated that strychnine could specifically block the action of
the inhibitory transmitter, glycine, which isaprominent neuro-
transmitter in the spinal cord (Werman et al., 1968; Young and Mac-
donald, 1983), this clearly represented an important mechanism
subserving the ability of strychnine to produce the spinal seizures
that Oaude Bernard first observed so long before. Several useful

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P. C. Jobe et al. (eds.), Neurotransmitters and Epilepsy
© Springer Science+Business Media New York 1987
216 Faingold

reviews on convulsant drugs have been published previously

(Hahn, 1960; Esplin and Zablocka-Esplin, 1969; Woodbury, 1980;
Davidoff, 1983).

2. Neurotransmitter Specificity
Extensive supporting evidence for the ability of drugs with con-
vulsant properties to affect the action of a specific neurotransmit-
ter continues tobe reported. Reports have appeared in recent years,
however, that suggest that the convulsant drugs produce effects
in addition to the neurotransmitter-specific actions in some CNS
regions or neuronal systems that appear to be quite important to
seizure induction. The effects of convulsant drugs are sometimes
reported to be dose-dependent in that a transmitter-specific effect
is observed at the lowest effective dose in some studies. However,
effects on the action of multiple neurotransmitters and even on
membrane properlies not directly related to neurotransmitter ac-
tion arealso observed (Freeman, 1973; Pellmar and Wilson, 1977a;
Barker and MacDonald, 1980; Rayport and Kandel, 1981; Heyer et
al., 1982). Another factor in establishing the mechanisms of seizure
induction that has not been considered sufficiently in many recent
investigations is that neurons in different regions of the mammalian
CNS are not affected to the same extent by convulsant drugs (Mac-
donald et al., 1979; Faingold and Stittsworth, 1980; see Faingold
et al., 1985a for review). Thus, the neuroanatomy of the CNS must
be prominently considered in attempting to understand the ability
of convulsant drugs to produce seizures.

3. Mode of Drug Administration

The technical question about how the drug gets to the neuron
must also be taken into account. Thus, systemic administration,
iontophoretic application, or administration of the agent into the
medium surrounding a neuron in vitro can each result in differen-
tial exposure of the cell body or cell processes of a neuron to the
convulsant drug. These differences can affect the magnitude and
even the nature of the effect observed (e.g., Faingold et al., 1984).
This dichotomy may result from the finding that ionic conductance
mechanisms that govern the excitability of the cell soma may dif-
fer from those that are predominant in cell processes even of the