Otenzepad

Otenzepad (AF-DX 116) is a selective and competitive M2 muscarinic acetylcholine receptor antagonist, with IC50 values of 640 nM and 386 nM for rabbit peripheral lung and rat heart, respectively[1].

Signaling Pathways >> Neuronal Signaling >> mAChR

Signaling Pathways >> GPCR/G Protein >> mAChR

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

640 nM (M2 muscarinic acetylcholine receptor in rabbit peripheral lung), 386 nM (M2 muscarinic acetylcholine receptor in rat heart)[1].

Otenzepad (0.5, 1 mg/kg, s.c., in rats) significantly improved win-stay acquisition relative to vehicle-injected controls[2]. Otenzepad (2 mg/kg, s.c., in rats) significantly improved retention relative to vehicle controls[2]. Otenzepad (0.3, 1.0, or 3.0 mg/kg, ip, in mice) potentiates the effects of glucose and reverses the effects of insulin on memory[3]. Animal Model: Forty-eight male Long-Evans rats (325-350 g)[2]. Dosage: 0.25, 0.5, 1.0 and 2.0 mg/kg. Administration: S.C. on the dorsum of the neck once. Result: Doses of 0.5 and 1.0 mg/kg significantly improved acquisition relative to vehicle controls, while doses of 0.25 and 2.0 mg/kg had no effect. Animal Model: Adult male Swiss mice (age 60–70 days; weight 25-30 g)[3]. Dosage: 0.3, 1.0, or 3.0 mg/kg. Administration: IP once. Result: Enhanced retention in an inverted-U dose–response manner, with significant enhancement seen at 1.0 mg/kg (U15,15 = 49, p < 0.02, compared with saline-saline-injected control group).

[1]. Bloom JW, et al. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116. Life Sci. 1987 Jul 27;41(4):491-6.

[2]. Packard MG, et al. Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory. Brain Res. 1990 Jul 30;524(1):72-6.

[3]. Kopf SR, et al. AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects of glucose and reverses the effects of insulin on memory. Neurobiol Learn Mem. 1998 Nov;70(3):305-13.

MOLECULAR FORMULA :

C24-H31-N5-O2

MOLECULAR WEIGHT :

421.60

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1533 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,30,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

83 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,30,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,30,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,30,1991