Table 3.

Anti-nociceptive and anti-inflammatory activities of EP receptor antagonists

Route/species	Experimental model	Noxious stimulus/site	Antagonist (nominal receptor)	Antagonist dosing	Efficacy	Reference
Oral
Guinea pig	Joint pain (mono-osteoarthritis)	Iodoacetate/shoulder joint	MF-498 (EP4)	30 mg·kg−1	+++	Clark et al. (2008)
	Thermal hyperalgesia	L-902688a/paw	MF-498 (EP4)	0.1–30 mg·kg−1	+++	Clark et al. (2008)
Rat	Writhing response	Acetic acid/peritoneal cavity	SC-19220 (EP1)	50–300 mg·kg−1	++	Drower et al. (1987)
	Behavioural response	Formalin/paw	SC-19220 (EP1)	50–150 mg·kg−1	++	Drower et al. (1987)
	Chronic mechanical/thermal hyperalgesia/allodynia	Nerve constriction/sciatic	ONO-8711 (EP1)	10–100 mg·kg−1 per day	+++	Kawahara et al. (2001)
	Chronic hyperalgesia (weight-bearing)	Freund's adjuvant/knee joint	GW-848687 (EP1)	30 mg·kg−1 per day	+++	Giblin et al. (2007)
	Chronic arthritis (oedema/radiology)	Freund's adjuvant/paw	Compound 20 (EP4)	0.005 mg·kg−1 per day	+++	Burch et al. (2008)
	Local oedema	Freund's adjuvant/paw	MF-266-1 (EP1)	Each 0.008–20 mg·kg−1 daily for 10 days	0	Clark et al. (2008)
			MF-266-3 (EP3)		0
			MF-498 (EP4)		+++
	Mechanical hyperalgesia	Carrageenan/paw	CJ-042794 (EP4)	1–30 mg·kg−1	+++	Murase et al. (2008a)
	Local oedema	Freund's adjuvant/paw	CJ-042794 (EP4)	1–30 mg·kg−1	+++	Murase et al. (2008a)
	Mechanical hyperalgesia	Carrageenan/paw	CJ-023423 (EP4)	3–100 mg·kg−1	+++	Nakao et al. (2007)
	Thermal hyperalgesia	PGE2/paw	CJ-023423 (EP4)	1–29 mg·kg−1	+++	Nakao et al. (2007)
	Chronic inflammation (weight-bearing)	Freund's adjuvant/paw	CJ-023423 (EP4)	10–57 mg·kg−1	+++	Nakao et al. (2007)
	Chronic inflammation (oedema, histology)	Freund's adjuvant/paw	CJ-023423 (EP4)	29–96 mg·kg−1	+++	Okumura et al. (2008)
Mouse	Writhing response	Phenylbenzylquinone/peritoneal cavity	SC-51089 (EP1)	1–30 mg·kg−1	+++	Hallinan et al. (1993)
	Writhing response	Phenylbenzylquinone/peritoneal cavity	SC-51322 (EP1)	1–30 mg·kg−1	+++	Hallinan et al. (1994)
	Migration of Langerhans cells into lymph node	Fluorescein isothiocyanate/skin	ONO-AE3-208 (EP4)	10 mg·kg−1 twice daily	++	Kabashima et al. (2003)
	Ear swelling/histology	UVB/skin of ear	ONO-AE3-208 (EP4)	10 mg·kg−1	++	Kabashima et al. (2007)
Intravenous
Rat	Sensory discharge	Acetic acid/bladder lumen	ONO-8711 (EP1)	1–3 mg·kg−1	++	Ikeda et al. (2006)
	Visceromotor reflex	Distension/bladder	DG-041 (EP3)	10 mg·kg−1	+++	Su et al. (2008a)
Intraperitoneal
Rat	Mechanical hyperalgesia	Freund's adjuvant/paw	AH-23848 (EP4)	0.1–10 mg·kg−1	+++	Lin et al. (2006)
	Thermal hyperalgesia	Freund's adjuvant/paw	AH-23848 (EP4)	0.1–10 mg·kg−1	+++	Lin et al. (2006)
Mouse	Mechanical allodynia	Sulprostone/intrathecal	ZM-325802 (EP1)	0.03 µg·kg−1	+++	Gil et al. (2008)
Topical to skin
Mouse	Oedema	Chronic UVB	ONO-8713 (EP1)	96 nmol	++	Tober et al. (2006)
Intraplantar
Rat	Paw-withdrawal	PGE2/pawb	SC-19220 (EP1)	2.3 nmol	++	Khasar et al. (1993)
	Mechanical hyperalgesia	Incision wound/paw	ONO-8711 (EP1)	4.5–114 nmol	+++	Omote et al. (2001)
	Chronic mechanical hyperalgesia	Partial nerve transection/sciatic	SC-19220 (EP1)	2.3 nmol	+++	Syriatowicz et al. (1999)
	Chronic thermal hyperalgesia	Partial nerve transection/sciatic	SC-19220 (EP1)	2.3 nmol	++	Syriatowicz et al. (1999)
Mouse	Mechanical allodynia	PGE2/paw	AH-6809 (EP1)	100 nmol	0	Kassuya et al. (2007)
			L-826266 (EP3)	0.1–10 nmol	+++
			L-161982 (EP4)	10 nmol	0
		Carrageenan/paw	L-826266 (EP3)	10 nmol	++	Kassuya et al. (2007)
			L-161982 (EP4)	10 nmol	++
	Paw-licking	PGE2/paw	AH-6809 (EP1)	10–100 nmol	0	Kassuya et al. (2007)
			L-826266 (EP3)	3–30 nmol	++
			L-161982 (EP4)	1–30 nmol	+++
Intrathecal
Rat	Mechanical allodynia	Nerve ligation/L5 spinal root	SC-51322 (EP1)	22–220 nmol	++	Hefferan et al. (2003); O'Reilly and Loomis (2007)
	Mechanical hyperalgesia	Incision wound/foot	ONO-8711 (EP1)	114–228 nmol	++	Omote et al. (2002)
	Thermal hyperalgesia	Incision wound/paw	ONO-8711 (EP1)	114–128 nmol	0	Ikeda et al. (2006)
	Flinching (late phase)	Formalin/paw	SC-58109 (EP1)	65–650 nmol	++	Malmberg et al. (1994)
	Mechanical hyperalgesia (late phase)	Carrageenan/paw	ONO-8711 (EP1)	2.28–228 nmol	+++	Nakayama et al. (2002)
	Mechanical hyperalgesia (late phase)	PGE2/intrathecal	ONO-8711 (EP1)	0.11–0.45 nmol	+++	Nakayama et al. (2004)
	Visceromotor reflex	Distension/bladder	L-798106 (EP3)	10–300 nmol	+++	Su et al. (2008b)
			DG-041 (EP3)	10–100 nmol	+++	Su et al. (2008b)
Mouse	Thermal hyperalgesia	PGE2/intrathecal	AH-6809 (EP1)	0.29–2.9 nmol	+++	Uda et al. (1990)
	Writhing response	PGE2/intrathecal	AH-6809 (EP1)	0.29–2.9 nmol	+++	Uda et al. (1990)
	Mechanical allodynia	PGE2/intrathecal	AH-6809 (EP1)	4.2 nmol	0	Minami et al. (1995)
	Thermal hyperalgesia	PGE2/intrathecalc	AH-6809 (EP1)	4.2 nmol	+++	Minami et al. (1995)
	Mechanical allodynia	PGE2/intrathecal	ONO-NT-012 (?)d	3 × 10−5–0.03 nmol	+++	Minami et al. (1995)
	Thermal hyperalgesia	PGE2/intrathecal	ONO-NT-012 (?)	3 × 10−5–0.03 nmol	0	Minami et al. (1995)
Topical to spinal tissue
Rat	Mechanical allodynia	Bicuculline/L5–L6 spine	SC-51322 (EP1)	0.22–17.5 nmol	+++	Zhang et al. (2001)

Upper and lower panels relate to parenteral and topical administration of antagonist.

^aSelective EP₄ agonist.

^bIntradermal.

^cAbout 30-fold higher dose of PGE₂ required compared with mechanical allodynia.

^dSee EP₁ antagonist section for specificity; reported pA₂ of 9.96 in allodynia model is unlikely to be valid because antagonist concentrations in biophase are unknown.