The antiepileptic activity of α-substituted acetamides, lactams, and cyclic imides
has been known for over six decades. We recently proposed an α-substituted amide group as
the minimum pharmacophore responsible for inhibition of neuronal nicotinic acetylcholine
receptors by these compounds, with the implication that inhibition of these receptors in the
brain might be the unifying mechanism of action for these classes of antiepileptic drugs. In
order to realize the pharmacological potential of these orally administered drugs, the relevant
aspects of solid-state chemistry and pharmaceutics (including solubility and stability) need to
be addressed. A better - more cohesive and generalized - understanding of the solid-state
properties of these drugs would pave the road for a rational approach to their development,
formulation, and manufacturing. In this paper, Pharmaceutically relevant aspects of the crystal
structure and solid-state chemistry of antiepileptic drugs containing the α-substituted
amide bond pharmacophore - α-substituted acetamides, lactams, and cyclic imides and the
structurally related barbiturates, hydantoins, and acetylureas are reviewed. The applicable experimental and computational
approaches are also briefly mentioned.
Keywords: Acetamides, lactams, cyclic imides, antiepileptic drugs, solid-state properties, crystal structure.
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