In certain embodiments, novel PAC1 receptor agonists are provided, wherein the agonist comprises a targeting sequence that binds to a PAC1 receptor, wherein the targeting sequence comprises a fragment of a maxadilan amino acid sequence. Linked to an amino acid sequence, wherein the targeting sequence comprises a full length 38 amino acid PACAP peptide or N-terminal fragment thereof containing the amino acid sequence HSDGIF, wherein the targeting sequence optionally includes an amino acid insertion in the PACAP peptide or Included between residue 11 and residue 12 of the fragment, fragments of the maxadilan amino acid sequence include fragments of the maxadilan sequence that are effective to activate PAC1 signaling.特定の実施形態では、新規ＰＡＣ１受容体作動薬が提供され、当該作動薬は、ＰＡＣ１受容体に結合する標的指向性配列を含み、上記標的指向性配列は、マキサジランアミノ酸配列の断片を含むアミノ酸配列に結び付けられており、標的指向性配列は、アミノ酸配列ＨＳＤＧＩＦを含有する完全長３８アミノ酸ＰＡＣＡＰペプチドまたはそのＮ末端断片を含み、上記標的指向性配列は場合によってアミノ酸挿入を上記ＰＡＣＡＰペプチドまたはその断片の残基１１と残基１２との間に含み、マキサジランアミノ酸配列の断片は、ＰＡＣ１シグナル伝達を活性化させるのに有効なマキサジラン配列の断片を含む。
