SER100TRISH [Ac-RYYRWKKKKKKK-NH2,
formerly ZP120] is a novel dodecapeptide with high affinity to the opioid
receptor like-1 (ORL1) receptor. The compound acts as a potassium and sodium
sparing aquaretic with mild vasodilatory properties and without CNS effects in
the expected therapeutic range [1]. Moreover, being a peptide analogue of the
endogen peptide nociceptin, SER100TRISH has been shown to have marked aquaretic
effects in vivo. However, in addition
to this effect SER100TRISH, at least during sodium replete conditions, seems to
induce an anti-natriuretic effect by an unknown mechanism.
SER100 was
acquired by Serodus from Zealand Pharma A/S in 2010. The development had been stopped
since SER100 unexpectedly induced a drop in systolic blood pressure and to a
lesser extent in diastolic pressure in patients with acute and chronic heart
failure. What Zealand Pharma regarded as a side effect Serodus saw as a potential
in patients with treatment resistant isolated systolic hypertension (TR-ISH)
[2].
Common Name: SER100TRISH
Synonyms: SER100TRISH; SER100; ZP120
IUPAC Name: -
CAS Number: -
Mechanism of Action: ORL1 partial agonist
Indication: Treatment
Resistant Isolated Systolic Hypertension
Development Stage: Phase II
Company: Serodus
ORL-1 is a
G-protein coupled receptor and promotes Ca2+ influx and K+
efflux. Another property of the receptor
is that it occurs presynaptically on a variety of neurons where it inhibits the
release of the respective neurotransmitter.
SER100 induces aquaresis by down-regulation of aquaporin-2 in the
kidneys and eliciting a mild vasodilatory response without reflex tachycardia
(no increase in heart rate). In animal
models the hypotensive effect of SER100 was not affected by other
antihypertensives, which predicts that SER100 will be effective as concomitant
treatment to products like furosemide, thiazides, beta-blockers, calcium
antagonists and ACE inhibitors [2].
Experimental results
strongly suggest a direct stimulatory effect of ZP120 on the Epithelial Na+
Channel in the kidney collecting ducts [3].
References:
1. Kapusta, D. R.; et.
al. Pharmacodynamic characterization of ZP120 (Ac-RYYRWKKKKKKK-NH2), a
novel, functionally selective nociceptin/orphanin FQ peptide receptor partial
agonist with sodium-potassium-sparing aquaretic activity. J Pharmacol Exp Ther 2005, 314(2), 652-660.
2. SER100TRISH
3. Petersen, J. S.; et. al. NOP receptor stimulation by ZP120 induces anti-natriuresis
through a direct effect on epithelial sodium channel (ENaC) in the renal
collecting duct. FASEB J 2008, 22 Meeting Abstract Supplement), 943.5.
