(S)-Nornicotine
Based on 1 Customer Validation
(S)-Nornicotine is a nicotine metabolite that crosses the blood-brain barrier. (S)-Nornicotine weakly inhibits human CYP2A6 with a Ki >300 μM. (S)-Nornicotine promotes dopamine release in rat striatal and nucleus accumbens slices and increases endogenous DOPAC overflow through a calcium-dependent nAChR pathway that is sensitive to Mecamylamine (HY-B1395A). (S)-Nornicotine reduces behavioral responses maintained by nicotine or sucrose, exerts analgesic effects in persistent inflammatory pain and neuropathic pain models, and enhances the analgesic effect of morphine. (S)-Nornicotine is useful for research on tobacco dependence and pain.
For research use only. We do not sell to patients.
- Purity : 98.59%
- CAS No.: 494-97-3
- Formula: C9H12N2
- Molecular Weight:148.21
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
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CYP2A6 ≥300 μM (Ki) |
Human Endogenous Metabolite |
In Vitro
(S)-Nornicotine (0.1-100 μM) induces a concentration-dependent and sustained overflow of endogenous DOPAC in a rat striatal brain slice perfusion model, with no significant desensitization[1].
(S)-Nornicotine (0.01-1.0 μM) does not modulate electrically stimulated overflow of endogenous DOPAC from superfused rat striatal slices[1].
(S)-Nornicotine (0.1-100 μM) induces a concentration-dependent tritium overflow in the perfusate of rat striatal brain slices preloaded with [3H]DA, which is consistent with a direct stimulatory effect on dopamine release[1].
(S)-Nornicotine (10-100 μM; 15 min) induces a calcium-dependent increase in endogenous DOPAC efflux in superfused rat striatal slices[1].
(S)-Nornicotine (0.02-400 μM; 10 min) is a weak inhibitor of CYP2A6-mediated coumarin 7-hydroxylation expressed in human lymphoblastoid cells, with a Ki value ≥300 μM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
(S)-Nornicotine (1-10 mg/kg; s.c.) dose-dependently decreases sucrose-maintained responding in rats, with potency comparable to that of R (+)-nornicotine[2].
(S)-Nornicotine (5.6-10 mg/kg; subcutaneous injection) dose-dependently reduces the duration of action of S (-)-nicotine self-administration[2].
(S)-Nornicotine (3-5.6 mg/kg; subcutaneous injection; once daily; for 10 consecutive days) persistently reduces S (-)-nicotine self-administration behavior in rats over 10 days without producing tolerance[2].
(S)-Nornicotine (5.6 mg/kg; subcutaneous injection; single dose) reaches a mean brain concentration of 214.6 ng/mL in rats, and its brain exposure is similar to that of R (+)-nornicotine[2].
(S)-Nornicotine (5.6 mg/kg; subcutaneous injection; once daily; for 9 consecutive days) causes sustained increases in blood pressure and heart rate in rats without producing tolerance[2].
(S)-Nornicotine (0.5-20 mg/kg; i.p.; single dose) produces dose-dependent inhibition of formalin-induced flinching behavior in both phases of the rat formalin test, with similar potency in phase 1 and phase 2 (ED50 approximately 1.5-1.8 mg/kg i.p.)[3].
(S)-Nornicotine (10-40 mg/kg; i.p.) produces moderate dose-dependent antinociception in the acute thermal paw test in rats, with an i.p. ED50 of 29.3 mg/kg[3].
(S)-Nornicotine (2.5-20 mg/kg; i.p.) produces motor side effects at doses above those required for analgesia, with tactile allodynia showing the greatest dose separation[3].
(S)-Nornicotine (2.5 mg/kg; 10-100 μg; i.p.; intrathecal injection) does not exhibit significant antinociceptive activity in the rat tail-flick test[3].
(S)-Nornicotine (2.5 mg/kg; 10-100 μg; i.p.; intrathecal injection) at sub-analgesic doses enhances the antinociceptive effect of morphine in the rat tail-flick test, and when administered intrathecally, the combination with morphine achieves approximately 100% of the maximum possible effect[3].
(S)-Nornicotine (0.01-7.5 mg/kg; i.p.; p.o.) at subanalgesic doses enhances the antihyperalgesic effect of morphine in the rat CCI model, achieving 100% MPE at the combination dose without motor impairment as assessed by the rotarod test[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; intravenous S(-)-nicotine self-administration model under FR5 20-sec signaled timeout schedule)[2]
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Dosage:1 mg/kg, 3 mg/kg, 5.6 mg/kg, 10 mg/kg
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Administration:s.c.; acute pretreatment 15 min before self-administration sessions; Latin Square within-subjects design
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Result:Decreased S(-)-nicotine self-administration in a dose-dependent manner, with significant decreases at 5.6 mg/kg and 10 mg/kg.
Did not significantly alter inactive lever responding.
Decreased responding throughout the entire 60-min session.
Showed lower potency than R(+)-nornicotine, with responding following 5.6 and 10 mg/kg significantly higher than following the same doses of R(+)-nornicotine.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; operant conditioning model with 45 mg sucrose pellet reinforcement under FR5 schedule)[2]
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Dosage:1 mg/kg, 3 mg/kg, 5.6 mg/kg, 10 mg/kg
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Administration:s.c.; acute pretreatment 15 min before sucrose responding sessions; Latin Square within-subjects design
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Result:Decreased sucrose-maintained responding in a dose-dependent manner.
Showed equipotency to R(+)-nornicotine with no enantioselectivity observed.
Affected specifically the active lever responding.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; intravenous S(-)-nicotine self-administration model under FR5 20-sec signaled timeout schedule)[2]
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Dosage:5.6 mg/kg, 10 mg/kg
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Administration:s.c.; acute pretreatment at 15, 60, 120, and 240 min before self-administration sessions; within-subjects randomized order
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Result:Produced a similar magnitude of decrease in S(-)-nicotine self-administration at 5.6 mg/kg as 3.0 mg/kg R(+)-nornicotine, with effect lasting up to 60 min.
Produced a similar magnitude of decrease in S(-)-nicotine self-administration at 10 mg/kg as 5.6 mg/kg R(+)-nornicotine, with effect lasting up to 240 min.
Exhibited a time-dependent loss of effect across increasing pretreatment intervals, with similar time course between enantiomers at equally effective doses.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; intravenous S(-)-nicotine self-administration model under FR5 20-sec signaled timeout schedule with repeated pretreatment)[2]
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Dosage:3 mg/kg, 5.6 mg/kg
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Administration:s.c.; once daily 15 min before self-administration sessions; 10 consecutive days
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Result:Decreased S(-)-nicotine self-administration compared to saline across all 10 sessions at both 3 mg/kg and 5.6 mg/kg.
Produced a greater decrease at 5.6 mg/kg than at 3 mg/kg on sessions 1-6.
Did not induce tolerance to the rate-decreasing effect across repeated pretreatments.
Showed a smaller decrease than 5.6 mg/kg R(+)-nornicotine on sessions 1, 3, and 6, with enantioselectivity dissipating across repeated treatments.
Resulted in continued decreased responding in the 5.6 mg/kg dose group on the first saline substitution session after termination, with no significant difference on the second saline session.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; brain pharmacokinetic assessment following acute systemic administration)[2]
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Dosage:5.6 mg/kg
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Administration:s.c.; single acute injection; terminal brain sampling at 60 min post-dose
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Result:Reached a mean brain concentration of 214.6 ng/mL 60 min after s.c. administration.
Showed brain levels not significantly different from brain levels of R(+)-nornicotine at the same dose and time point.
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Animal Model:Sprague-Dawley (male; 230-300 g at start; prior history of nornicotine treatment; minimum 14 drug-free days before testing; cardiovascular function assessment via radiotelemetry following repeated administration)[2]
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Dosage:5.6 mg/kg
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Administration:s.c.; once daily; 9 consecutive days; 2-hr cardiovascular recording post-injection each day
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Result:Increased mean arterial blood pressure (MAP) and heart rate acutely on Day 1.
Did not induce tolerance to the MAP-elevating effect across 9 days of repeated treatment, with MAP remaining significantly elevated relative to saline control on Day 9.
Did not induce tolerance to the heart rate-elevating effect across 9 days of repeated treatment, with heart rate remaining significantly elevated relative to saline on Day 9.
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; subcutaneous injection of 50 μL 5% formalin into dorsal surface of left hind paw)[3]
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Dosage:0.5, 2.5, 5, 10, 20 mg/kg
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Administration:i.p.; 15 min prior to formalin injection; single dose
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Result:Inhibited formalin-induced flinching in both the early (0-10 min) and late (20-60 min) phases in a dose-related manner.
Had an ED50 of 1.8 mg/kg i.p. for the 1st phase.
Had an ED50 of 1.5 mg/kg i.p. for the 2nd phase.
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; intact; thermal plantar test using radiant heat)[3]
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Dosage:10, 20, 30, 40 mg/kg
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Administration:i.p.; randomized doses with weekly intervals between treatments
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Result:Caused a dose-dependent increase in paw withdrawal latency, with an ED50 of 29.3 mg/kg i.p.
Could not be tested at doses above 40 mg/kg i.p. due to toxicity.
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; intact; motor side effect assessment via rotarod, locomotor activity, ataxia, activity level)[3]
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Dosage:2.5, 5, 10, 20 mg/kg
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Administration:i.p.; randomized doses with 48 h intervals (rotarod)
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Result:Caused dose-related motor incoordination on the rotarod, with an ED50 of 13.6 mg/kg i.p.
Did not produce a statistically significant decrease in locomotor activity compared to saline.
Produced dose-related ataxia.
Produced dose-related decreases in overall activity level.
Had less pronounced ataxia and activity level decreases than the R(+)-enantiomer.
Had a therapeutic index ratio (ED50 rotarod / ED50 analgesia) of ~3 for mechanical hyperalgesia.
Had a therapeutic index ratio of ~90 for tactile allodynia.
Had a therapeutic index ratio of ~9 for formalin 2nd phase flinching.
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; intact; tail-flick test using thermal stimulation; some with chronic spinal subarachnoid catheterization)[3]
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Dosage:2.5 mg/kg (i.p.); 10, 30, 100 μg (i.t.)
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Administration:i.p.; i.t.
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Result:Had no antinociceptive activity on its own at 2.5 mg/kg i.p.
Did not produce significant antinociception across the 10-100 μg i.t. dose range, with %MPE values remaining near the saline level (~10% or less).
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; intact; tail-flick test; some with chronic spinal subarachnoid catheterization; this compound in combination with morphine)[3]
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Dosage:2.5 mg/kg (i.p., combined with 3 mg/kg morphine i.p.); 10, 30, 100 μg (i.t., combined with 0.5 μg morphine i.t.)
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Administration:i.p. (combination with morphine); i.t. (combination with morphine)
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Result:Enhanced the antinociception produced by 3 mg/kg morphine i.p. at a sub-analgesic dose of 2.5 mg/kg i.p. in the tail-flick test.
Enhanced the effectiveness of this compound at doses that had no antinociceptive activity alone when combined with 0.5 μg morphine i.t.
Achieved a maximum effect of ~100% MPE with the combination of 0.5 μg morphine i.t. and 100 μg this compound i.t.
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Animal Model:Sprague-Dawley (male; ~90 days old; ~350 g; chronic constriction nerve injury;this compound in combination with morphine)[3]
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Dosage:0.01, 0.05, 0.1, 0.5 mg/kg (i.p., combined with 3 mg/kg morphine i.p.); 0.1, 0.5, 1, 5, 7.5 mg/kg (p.o., combined with 5 mg/kg morphine p.o.)
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Administration:i.p. (combination with morphine); p.o. (combination with morphine)
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Result:Produced dose-related antihyperalgesia in the presence of low-dose morphine via both i.p. and p.o. routes at doses with no significant antihyperalgesic activity alone.
Achieved maximum efficacy of 100% MPE with 0.5 mg/kg this compound i.p. plus 3 mg/kg morphine i.p.
Achieved maximum efficacy of 100% MPE with 7.5 mg/kg this compound p.o. plus 5 mg/kg morphine p.o.
Showed no motor effect at the combination doses tested on the rotarod: 3 mg/kg this compound i.p. plus 3 mg/kg morphine i.p., and 7.5 mg/kg this compound p.o. plus 5 mg/kg morphine p.o., as rats remained on the rotarod for the full 180 s cut-off.
Chemical Information
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CAS No. 494-97-3
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Appearance Liquid (Density: 1.044 g/cm3)
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Molecular Weight 148.21
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Formula C9H12N2
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Color Light yellow to brown
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SMILES
C1([C@H]2NCCC2)=CC=CN=C1
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Structure Classification
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Initial Source
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (674.72 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (16.87 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (16.87 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Formalin-Induced Paw Inflammation/Nociceptive Inflammation
The formalin-induced paw inflammation/nociceptive test is a chemical persistent pain model in rodents in which subcutaneous injection of formalin into the hind paw produces spontaneous nocifensive behaviors such as flinching and licking. The response is classically biphasic, consisting of an early acute phase (Phase I) reflecting direct activation of peripheral nociceptors (particularly C-fiber afferents), followed by a later prolonged phase (Phase II) associated with central sensitization in the spinal dorsal horn driven by sustained afferent input and inflammatory signaling. This model is widely used to evaluate analgesic and anti-inflammatory interventions because it captures both peripheral nociception and central sensitization processes within a single assay system.
Purity & Documentation
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Data Sheet (308 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 6.7472 mL | 33.7359 mL | 67.4718 mL | 168.6796 mL |
| 5 mM | 1.3494 mL | 6.7472 mL | 13.4944 mL | 33.7359 mL | |
| 10 mM | 0.6747 mL | 3.3736 mL | 6.7472 mL | 16.8680 mL | |
| 15 mM | 0.4498 mL | 2.2491 mL | 4.4981 mL | 11.2453 mL | |
| 20 mM | 0.3374 mL | 1.6868 mL | 3.3736 mL | 8.4340 mL | |
| 25 mM | 0.2699 mL | 1.3494 mL | 2.6989 mL | 6.7472 mL | |
| 30 mM | 0.2249 mL | 1.1245 mL | 2.2491 mL | 5.6227 mL | |
| 40 mM | 0.1687 mL | 0.8434 mL | 1.6868 mL | 4.2170 mL | |
| 50 mM | 0.1349 mL | 0.6747 mL | 1.3494 mL | 3.3736 mL | |
| 60 mM | 0.1125 mL | 0.5623 mL | 1.1245 mL | 2.8113 mL | |
| 80 mM | 0.0843 mL | 0.4217 mL | 0.8434 mL | 2.1085 mL | |
| 100 mM | 0.0675 mL | 0.3374 mL | 0.6747 mL | 1.6868 mL |
(S)-Nornicotine Related Classifications
HY-W040430 Related Classifications
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