Table 1. Specific and nonspecific modulators of adrenomedullin-induced effects.

Target	Drug	Mode of action/biological activity	Side-effects/disadvantages	Antiangiogenic potential	Reference
Specific modulators of AM-induced effects
Ligand (adrenomedullin)	AM mRNA rybozyme	AM mRNA degradation	Lack of reliable targeted delivery	Not tested	Taylor and Samson (2002)
	AMBP-1 (binding protein)	Affinity to receptor is unaltered Protection of peptide from degradation by proteases	Not tested	Not tested	Reviewed by Zudaire et al (2003)
	Anti-AM blocking antibody	Inhibition of AM activity	Not tested	Decreased mean vessel area in tumour xenografts	Ouafik et al (2002)
	Positive nonpeptidic regulators	Binding to AM	Vasodilation in vivo	Not tested	Martinez et al (2004a), (2004b)
	Negative nonpeptidic regulators	Binding to AM	Vasoconstriction	Not tested	Martinez et al (2004a), (2004b)
Receptor	Fragmentary peptides
	AM22-52 (receptor antagonist) CGRP8-37 (receptor antagonist)	Competition with ligand for binding to the receptor	Short half-life Short half-life	Not tested Not tested	Poyner et al (2002) Poyner et al (2002)
	Anti-CL blocking antibody Anti-RAMPs blocking antibodies	Direct interaction with receptor has been suggested	Not tested Not tested	Inhibit HUVEC migration and capillary tube formation in vitro	Fernandez-Sauze et al (2004)
Nonspecific modulators of AM-induced effects
Signalling cascades (secondary messengers)	Wortmannin (PI3K inhibitor) PD98059 (MAPK inhibitors)	Inhibition of ligand-induced phospohorylation of secondary messengers/kinases	Nonspecific Nonspecific	Prevent angiogenesis in vitro and in vivo	Kim et al (2003) Kim et al (2003)
Unknown	Vinblastine	Interaction with cytoskeleton	Nonspecific	Interruption of AM-induced capillary-like tube formation	Ribatti et al (2003)