Abstract Tizanidine is a centrally acting imidazoline derivative with a novel mechanism of action, closely resembling clonidine in its structure and pharmacological mechanism. Tizanidine has Federal Drug Agency (FDA) approval for the use of muscle spasticity and/or musculoskeletal pain, however, sometimes used off label in the treatment of trigeminal neuralgia and tension headaches. Although clonidine and associated structurally similar compounds (e.g., brimonidine, guanfacine, and tetrahydrozoline) exposures are more reported, unintentional and intentional exposures of tizanidine are sparsely found in the literature, and many of these case reports and treatment are an extrapolation of clonidine overdose given their structural and pharmacologic resemblance.