Minocycline exerts acute inhibitory effects on cerebral cortex excitability in humans

Minocycline 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 4h after a single oral dose of 200mg 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.