Results of the two-and-a-half-year study were today published in the online edition of Nature, the international scientific journal.
"This also provides hope for those with traumatic head injuries - the brain mechanisms of repair are similar so there is potential for this to work for them too," study co-author Dr Andrew Clarkson said.
Dr Clarkson (31), a research fellow at the Otago University departments of psychology and anatomy and structural biology, says human trials using the drug compounds could begin within two years.
One compound - known to enhance cognition and initially developed to treat Alzheimer's disease - is already being trialled in people with learning difficulties.
In the first study of its kind, Dr Clarkson and colleagues at the University of California, including neurologist co-author Dr Thomas Carmichael, found the compound, when administered to mice in slow-release doses, reactivated neurons in the brain responsible for limb function.
These neurons had initially appeared to be dead or dormant after a stroke.
Six weeks of treatment produced dramatic results, with an extra 50% of gross motor limb mobility consistently gained.
Treatment of the mice began three days after the stroke event - the equivalent of about three weeks in humans.
Dr Clarkson said this was a "tremendous finding".
"This could potentially be the biggest therapeutic breakthrough in many years," he said.
"To see the dramatic gain of function was unexpected.
"I'm still shocked at what we found.
"I repeated the initial study myself three times before I felt confident that it was real."
The treatment worked on gross motor skills, but it would take further research to clarify whether the drug could also help with the fine motor skills associated with speech.
This class of drugs, known as "extrasynaptic GABA inverse agonists", was not yet sufficiently advanced to be used on a prolonged basis in humans, because of known side-effects on the kidneys.
Once this problem had been resolved, it should be possible for stroke victims to use the drug as part of a clinical trial, he said.
This novel research is likely to result in a major rethink about several pieces of long-held received wisdom about the brain.
The research suggests that some brain cells affected by strokes or other head injuries have not been killed, as often previously thought, but are effectively "sleeping" and can be reactivated.
Much of the previous therapeutic emphasis has been on rapidly administering clot-busting drugs within a few hours, at most, of a stroke, while the new approach is intended to be used weeks later.
