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Several small molecule CGRP receptor antagonists have now been reported and their effects profiled in a variety of in vivo assays. Of particular interest is the observation that some antagonists display marked species selectivity. Doods and coworkers[1] reported that BIBN4096BS exhibited 200-fold higher affinity for human and marmoset CGRP receptors, than for receptors from rat, dog, guinea pig and rabbit. In addition, Edvinsson and colleagues[2] reported that compound 1 was a significantly more potent antagonist on human cerebral arteries than on guinea pig arteries. In the present study, we sought to identify the molecular basis for this profound species selectivity.

Pharmacological Differences between Human and Rat CGRP Receptors Are Determined by RAMP1