Methylprednisolone (Depo-Medrol, Medrol, Solu-Medrol) is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally. Regardless of route of administration, methylprednisolone integrates systemically as exhibited by its effectiveness to quickly reduce inflammation during acute flares. It is associated with many adverse reactions that require tapering off the drug as soon as the disease is under control. Serious side effects include iatrogenic Cushing's Syndrome, hypertension, osteoporosis, diabetes, infection, and skin atrophy. Chemically, methylprednisolone is a synthetic pregnane steroid hormone derived from hydrocortisone and prednisolone. It belongs to a class of synthetic glucocorticoids and more generally, corticosteroids. It acts as a mineralocorticoid and glucocorticoid receptor agonist. In comparison to other exogenous glucocorticoids, methylprednisolone has a higher affinity to glucocorticoid receptors than to mineralocorticoid receptors. Glucocorticoid's name was derived after the discovery of their involvement in regulating carbohydrate metabolism. The cellular functions of glucocorticoids, such as methylprednisolone, are now understood to regulate homeostasis, metabolism, development, cognition, and inflammation. They play a critical role in adapting and responding to environmental, physical and emotional stress. Methylprednisolone was first synthesized and manufactured by The Upjohn Company (now Pfizer) and FDA approved in the United States in October 1957. In 2020, it was the 161st most commonly prescribed medication in the United States, with more than 3million prescriptions. Methylprednisolone is also on the World Health Organization's List of Essential Medicines for its effects against lymphoid leukemia. Pharmacodynamics Methylprednisolone is a synthetic glucocorticoid (GCs) that exhibits pleiotropic effects on a variety of physiological mechanisms. However, they have been prescribed extensively for their effects on inflammation and immunity. The effects of synthetic glucocorticoids, such as methylprednisolone, is dependent on its association with intracellular glucocorticoid receptors (GRs), and to a lesser extent, mineralocorticoid receptors (MRs). GRs are widely distributed in contrast to MRs that show a restricted tissue distribution. By this mechanism, the ligand-bound receptor translocate to the nucleus and modulate gene expression. Signal transduction In the absence of endogenous or synthetic GCs, monomeric GRs are located in the cytoplasm and form multiprotein complexes with heat shock proteins (HSPs), immunophilins, and other chaperones such as src, and p23. The GR acts in a ligand-dependent manner, with the complex holding the GR in an inactive form with high specificity for the