The histamine H₄ receptor (H₄R) is expressed in several cell types of the immune system and is assumed to play an important pro-inflammatory role in various diseases, including bronchial asthma, atopic dermatitis, and pruritus. Accordingly, H₄R antagonists have been suggested to provide valuable drugs for the treatment of these diseases. Over the past decade, the indole derivative 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine (JNJ7777120) has become the “standard” H₄R antagonist and has been extensively used to assess the pathophysiological role of the H₄R. However, the situation has now become more complicated by recent data (p. 749 and Naunyn Schmiedebergs Arch Pharmacol doi: 10.1007/s00210-011-0612-3) showing that JNJ7777120 can also activate β-arrestin in a supposedly G_i-protein-independent (pertussis toxin-insensitive) manner and that at certain H₄R species orthologs, JNJ7777120 exhibits partial agonist efficacy with respect to G_i-protein activation (steady-state high-affinity GTPase activity). These novel findings can be explained within the concept of functional selectivity or biased signaling, assuming unique ligand-specific receptor conformations with distinct signal transduction capabilities. Thus, great caution must be exerted when interpreting in vivo effects of JNJ7777120 as H₄R antagonism. We discuss future directions to get out of the current dilemma in which there is no “standard” H₄R antagonist available to the scientific community.

Fraudulent papers from paper mills are a serious threat to the entire scientific community. Naunyn-Schmiedeberg’s Archives of Pharmacology has become the target of a massive attack of fraudulent papers originating from paper mills. This editorial highlights 20 important features we observed with paper mills and explains how the journal is responding to this serious threat to restore the integrity of science. Hopefully, this editorial is also helpful for editors of other scientific journals.