modafinil + propranolol

Modafinil + propranolol is a combination of two small molecule drugs, modafinil and propranolol. Modafinil is a wakefulness-promoting agent and central nervous system (CNS) stimulant primarily used to treat excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work disorder. Its mechanism involves inhibition of dopamine reuptake by binding to the dopamine transporter, leading to increased extracellular dopamine levels; it also activates glutamatergic circuits while inhibiting GABAergic neurotransmission. Propranolol is a nonselective beta-adrenergic receptor antagonist (beta blocker) indicated for hypertension, angina pectoris, arrhythmias, migraine prophylaxis, essential tremor, and other cardiovascular conditions. It works by blocking beta-1 and beta-2 adrenergic receptors in the heart and vasculature. The combination has been studied experimentally—for example in postural orthostatic tachycardia syndrome (POTS)—to assess whether propranolol can mitigate potential heart rate increases caused by modafinil while preserving cognitive benefits[3]. There is a moderate drug interaction between these agents because modafinil inhibits CYP2C19-mediated metabolism of propranolol; this may increase circulating levels of propranolol[1][2][5]. The combination should be used with caution under medical supervision.