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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12N2
Molecular Weight 148.205
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORNICOTINE

SMILES

C1CN[C@@H](C1)C2=CN=CC=C2

InChI

InChIKey=MYKUKUCHPMASKF-VIFPVBQESA-N
InChI=1S/C9H12N2/c1-3-8(7-10-5-1)9-4-2-6-11-9/h1,3,5,7,9,11H,2,4,6H2/t9-/m0/s1

HIDE SMILES / InChI

Molecular Formula C9H12N2
Molecular Weight 148.205
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Nornicotine is a natural alkaloid produced by plants in the genus Nicotiana and is structurally related to nicotine. Nornicotine is the direct precursor of tobacco-specific nitrosamine N'-nitrosonornicotine, which is a highly potent human carcinogen. Nornicotine is an active nicotine metabolite, which accumulates in brain to pharmacologically relevant concentrations following repeated nicotine administration to rats. Nornicotine stimulated DA release from nucleus accumbens in a nicotinic receptor-mediated manner, further supporting the hypothesis that nornicotine contributes to tobacco dependence. Nornicotine is present in Nicotiana tobaccum in both S(-) and R(+) enantiomeric forms. Nornicotine enantiomeric forms appear to differ in analgesic potency and side effects. Exposure to nornicotine results in additional activation of α7-type receptors, which may be important for effects on cognition and attention. Likewise, the effects of nornicotine on α6-containing receptors may contribute to the reinforcing effects of nicotine, and therefore, is relevant to dependence on tobacco. In contrast to nicotine, nornicotine had relatively low activity on receptors other than those containing α7 or α6 subunits. Yaupon Therapeutics was developing Nornicotine as a once a day oral drug for smoking cessation. However this development was discontinued.

CNS Activity

Originator

Approval Year

PubMed

Sample Use Guides

In Vivo Use Guide
Rats: 5 mg/kg s.c. The 5 mg/kg dose was chosen based on a previous report suggesting that this dose was behaviorally active.
Route of Administration: Other
In Vitro Use Guide
The effects of nornicotine on specific combinations of neuronal nicotinic acetylcholine receptor (nAChR) subunits expressed in Xenopus oocytes were studied. Of the nAChR subtypes studied, it was found that α7 receptors were very responsive to nornicotine (EC50≈ 17 uM Imax 50% compared to ACh). nAChRs containing the ligand-binding domain of the α6 subunits (in the form of an α6/α3 chimera) were also strongly responsive to nornicotine (EC50≈ 4 uM Imax50% compared to ACh).
Substance Class Chemical
Record UNII
83H6L5QD8Z
Record Status Validated (UNII)
Record Version