While semi-synthetic ion channels, often based on modified peptidic channels like gramicidin, had been prepared since the 1970s, the first attempt to prepare a synthetic ion channel was made in 1982 using a substituted β-cyclodextrin.
Inspired by gramicidin, this molecule was designed to be a barrel-shaped entity spanning a single leaflet of a bilayer membrane, becoming "active" only when two molecules in opposite leaflets come together in an end-to-end fashion. While the compound does induce ion-fluxes in vesicles, the data does not unambiguously show channel formation (as opposed to other transport mechanisms; see Mechanism).
Na transport by such channels was first reported by two groups of investigators in 1989–1990.
With the adoption of voltage clamp technique to synthetic channel research in the early 1990s, researchers were able to observe quantized electrical activities from synthetic molecules, often considered the signature evidence for ion channels.  This led to a sustained increase in research activity over the next two decades.  In 2009, over 25 peer-reviewed papers were published on the topic, and a series of comprehensive reviews are available.