Minocycline exerts acute inhibitory effects on cerebral cortex excitability in humans

• Minocycline bears a promising potential as a possible therapeutic agent in epilepsy.
• Acute effects of minocycline on cortical excitability in humans can be tested with transcranial magnetic stimulation (TMS).
• In a randomised, double-blind, placebo-controlled cross-over study we found that minocycline prolonged cortical silent periods.
• This demonstrates that cortical inhibition is rapidly increased after a single oral dose of minocycline in humans.

SummaryMinocycline has efficacy to alleviate seizure activity in animal models of epilepsy. Among other mechanisms it has been postulated that minocycline can inhibit microglial activation and develop beneficial effects by decreasing glutamate excitotoxicity. To explore acute effects of minocycline on human motor cortex excitability we used single- and paired-pulse transcranial magnetic stimulation in 12 healthy subjects 4 h after a single oral dose of 200 mg minocycline or placebo was administered in a randomised, double-blind, placebo-controlled crossover design. Mean cortical silent period, an inhibitory parameter of predominantly intracortical origin, was prolonged after minocycline compared to placebo, while other TMS parameters of cortical excitability remained unchanged. The results demonstrate that a particular parameter of cortical inhibition is rapidly increased after a single oral dose of minocycline in humans.