peripherally selective drug peripherally selective drug peripherally selective drugs have their primary mechanism of action outside of the central nervous system (cns), usually because they are excluded from the cns by the blood–brain barrier. by being excluded from the cns, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. for example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. these peripherally selective opioids can be used as antidiarrheals, for instance loperamide (imodium). mechanisms of peripheral selectivity include physicochemical hydrophilicity and large molecular size, which prevent drug permeation through the lipid bilayer cell membranes of the blood–brain barrier, and efflux out of the brain by blood–brain barrier transporters such as p-glycoprotein among many others. transport out of the brain by p-glycoprotein is thought to be responsible for the peripheral selectivity of many drugs, including loperamide, domperidone, fexofenadine, bilastine, cetirizine, ivermectin, and dexamethasone, among others. examples α-methylserotonin – a serotonin receptor agonist alvimopan – a μ-opioid receptor antagonist used in the treatment of postoperative ileus anastrozole – an aromatase inhibitor used in the treatment of breast cancer atenolol – a beta blocker benserazide – an aromatic l-amino acid decarboxylase inhibitor used in combination with levodopa in the treatment of parkinson's disease bethanechol – a muscarinic acetylcholine receptor agonist used in the treatment of dry mouth and urinary retention bicalutamide – an antiandrogen with peripheral selectivity in animals but seemingly not in humans bilastine – a non-sedating antihistamine bisoprolol – a beta blocker carbachol – a non-selective acetylcholine receptor agonist used in the treatment of glaucoma carbidopa – an aromatic l-amino acid decarboxylase inhibitor used in combination with levodopa in the treatment of parkinson's disease cetirizine – a non-sedating antihistamine colchicine – an alkaloid and tubulin polymerization inhibitor used to treat gout darolutamide – an antiandrogen used in the treatment of prostate cancer desloratadine – a non-sedating antihistamine dexamethasone – a glucocorticoid with some peripheral selectivity digoxin – a cardiac glycoside and sodium–potassium pump inhibitor domperidone – a d2 receptor antagonist used as an antiemetic, gastroprokinetic agent, and galactogogue dopamine – a dopamine receptor agonist used as a cardiac stimulant and positive inotropic agent eluxadoline – a μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist used in the treatment of diarrhea-predominant irritable bowel syndrome epinephrine (adrenaline) – an adrenergic receptor agonist used as a cardiac stimulant and in the treatment of anaphylaxis fenoldopam – a d1 receptor agonist used as an antihypertensive agent fexofenadine – a non-sedating antihistamine fulvestrant – an antiestrogen used in the treatment of breast cancer gaba – a dietary supplement glycopyrronium bromide – an anticholinergic hyoscine butylbromide – an anticholinergic itopride – a d2 receptor antagonist and acetylcholinesterase inhibitor used as a gastroprokinetic agent ivermectin – an antiparasitic labetalol – a beta blocker levocetirizine – a non-sedating antihistamine loperamide – a μ-opioid receptor agonist used as an antidiarrheal loratadine – a non-sedating antihistamine methacholine – a choline ester and muscarinic acetylcholine receptor agonist methylhomatropine – an anticholinergic methylnaltrexone – a μ-opioid receptor antagonist used in the treatment of opioid-induced constipation metopimazine – a d2 receptor antagonist used in the treatment of nausea, vomiting, and gastroparesis midodrine – an α1-adrenergic receptor agonist used in the treatment of orthostatic hypotension nadolol – a beta blocker naloxegol – a μ-opioid receptor antagonist used in the treatment of opioid-induced constipation norepinephrine (noradrenaline) – an adrenergic receptor agonist ondansetron – a 5-ht3 receptor antagonist with some peripheral selectivity peptides and proteins (e.g., insulin, oxytocin, vasopressin, opioid peptides, growth factors, many others) pirenzepine – an anticholinergic pyridostigmine – an acetylcholinesterase inhibitor and parasympathomimetic serotonin – a serotonin receptor agonist sotalol – a beta blocker terfenadine – a non-sedating antihistamine timepidium bromide – an anticholinergic trimetaphan camsilate – a nicotinic acetylcholine receptor antagonist trospium chloride – an anticholinergic vinblastine – a vinca alkaloid and antineoplastic agent