RVD-Hpα (pepcan-12) is an endogenous neuropeptide found in human and mammalian brain, which was originally proposed to act as a selective agonist for the CB1 cannabinoid receptor.
[2] Recently it was shown that RVD-Hpα (also called Pepcan-12) is a potent negative allosteric modulator at CB1 receptors, together with other newly described N-terminally extended peptides (pepcans).
This peptide is very specifically expressed in the noradrenergic neurons in the brain, mainly the locus coeruleus and its projections and in the adrenal medulla.
[5] RVD-Hpα also significantly potentiated the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for GTPγS binding and cAMP inhibition (5–10 fold).
RVD-Hpα was increased upon endotoxemia and ischemia reperfusion damage where CB2 receptors play a protective role.