Mast cells—the immune cells involved in allergic reactions—are usually activated by antibodies. But mast cells can also respond to cationic substances, including drugs, in what are called pseudoallergic reactions. A team of researchers led by Xinzhong Dong of Johns Hopkins University School of Medicine has identified the receptor protein on mast cells that’s responsible for these pseudoallergic drug reactions (Nature 2014, DOI: 10.1038/nature14022). In mice, a receptor called Mrgprb2 is responsible for histamine release, inflammation, and airway contraction. The team noted that mutant mice without the receptor had none of these responses. The mouse receptor is an analog of the human receptor MRGPRX2. The researchers discovered that many small-molecule drugs containing a tetrahydroisoquinoline unit target the receptor. Drugs with this motif include neuromuscular blocking drugs and the fluoroquinolone class of antibiotics. Dong and coworkers suggest the new information can be used during drug discovery to screen out compounds that are likely to trigger pseudoallergic reactions.