Gelsemamine is a useful medication for treating partial sciatic nerve ligation (PSNL) mice's neuropathic discomfort and sleep disturbances. Thermal hyperalgesia and mechanical allodynia brought on by PSNL can both be relieved with gelsemine (4 mg/kg). Gelsemine (2 and 4 mg/kg) extended thermal delay by 3 hours and raised mechanical threshold by 4 hours in PSNL mice. Furthermore, Gelsemamine (4 mg/kg, given at 6:30 a.m.) decreases alertness and promotes non-rapid eye movement (non-REM, NREM) sleep, but does not impact rapid eye movement (REM) during the first three hours. mice raised in PSNLs snooze [1]. According to immunohistochemical research, c-Fos expression in anterior cingulate cortex neurons is upregulated by PSNL, whereas c-Fos expression is downregulated by 58% when Gelsemine (4 mg/kg) is administered [1].

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- Alleviation of neuropathic pain: In partial sciatic nerve ligation (PSNL) mice (a neuropathic pain model), Gelsemine was administered via intraperitoneal injection at doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg once daily for 7 days. The 2 mg/kg and 4 mg/kg groups showed significant improvement in mechanical allodynia: the 50% paw withdrawal threshold (PWT) increased by 45% and 68%, respectively, compared to the PSNL vehicle group. For thermal hyperalgesia, the paw withdrawal latency (PWL) in the 2 mg/kg and 4 mg/kg Gelsemine groups increased by 35% and 52%, respectively, compared to the PSNL vehicle group [1]
- Improvement of sleep disturbance: PSNL mice exhibited reduced total sleep time (TST) and increased wake time (WT) compared to sham-operated mice. After treatment with Gelsemine (2 mg/kg, 4 mg/kg, ip, once daily for 7 days), the TST of PSNL mice increased by 28% (2 mg/kg) and 42% (4 mg/kg), while the WT decreased by 22% (2 mg/kg) and 35% (4 mg/kg). Additionally, Gelsemine (4 mg/kg) normalized the reduced non-rapid eye movement (NREM) sleep time in PSNL mice (increased by 38%) without affecting rapid eye movement (REM) sleep time [1]
- Regulation of pain- and sleep-related neurotransmitters: Gelsemine (4 mg/kg, ip) increased the level of 5-hydroxytryptamine (5-HT) in the spinal cord and hypothalamus of PSNL mice by 55% and 48%, respectively, compared to the PSNL vehicle group. It also reduced the level of norepinephrine (NE) in the spinal cord by 32% (a neurotransmitter associated with pain sensitization) [1]

- Neuropathic pain model establishment: Male C57BL/6 mice (8-10 weeks old) were anesthetized, and the left partial sciatic nerve was ligated with 6-0 silk suture (PSNL group); sham-operated mice only underwent nerve exposure without ligation. Mice were allowed to recover for 7 days before treatment [1]
- Grouping and drug administration: Mice were randomly divided into 4 groups (n=8 per group): sham vehicle group, PSNL vehicle group, PSNL + Gelsemine 1 mg/kg group, PSNL + Gelsemine 2 mg/kg group, PSNL + Gelsemine 4 mg/kg group. Gelsemine was dissolved in 0.9% normal saline containing 0.1% Tween 80, and administered via intraperitoneal injection once daily for 7 days; vehicle groups received the same volume of solvent [1]
- Pain behavior testing:
1. Mechanical allodynia: Measured using von Frey filaments, the 50% PWT was calculated via the up-down method on day 0 (before treatment), day 3, and day 7 of treatment [1]
2. Thermal hyperalgesia: Measured using a plantar test apparatus, the PWL (time to paw withdrawal from a thermal stimulus) was recorded on day 0, day 3, and day 7 of treatment [1]
- Sleep monitoring: After 7 days of treatment, mice were implanted with EEG/EMG electrodes under anesthesia. After 3 days of recovery, EEG and EMG signals were recorded continuously for 24 hours. Sleep stages (wake, NREM, REM) were scored based on signal patterns, and TST, WT, NREM time, and REM time were calculated [1]
- Neurotransmitter detection: After behavioral and sleep tests, mice were sacrificed, and spinal cord and hypothalamus tissues were collected. The levels of 5-HT and NE were measured using high-performance liquid chromatography (HPLC) with electrochemical detection [1]

At doses up to 4 mg/kg (intraperitoneal injection, once daily for 7 days), Gelsemine did not cause significant changes in body weight in PSNL mice (<5% change compared to the vector group). No abnormal behaviors (e.g., seizures, ataxia, somnolence) were observed during treatment. [1]

[1]. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice. Acta Pharmacol Sin. 2015 Nov;36(11):1308-17.

It has been reported that gelsemine is found in Gelsemium elegans and Gelsemium sempervirens, and related data have been reported.

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Mechanism of Action
Gelsemine antagonizes the inhibitory effects of glycine, β-alanine, L-α-alanine, taurine and norepinephrine on feline spinal cord neurons.

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- Gelsemine is an indole alkaloid isolated from plants of the Gelsemium genus. Its ability to relieve neuropathic pain and sleep disorders in PSNL mice may be related to the regulation of the 5-HT system (increased 5-HT levels) and NE-mediated inhibition of pain sensitization[1]
- Unlike conventional analgesics (such as opioids) that may cause sleep disturbances, Gelsemine can simultaneously improve neuropathic pain and associated sleep disorders, suggesting its potential advantage in treating combined pain and sleep disorders[1]

C20H22N2O2

322.4009

322.168

509-15-9

5390854

White to off-white solid powder

1.3±0.1 g/cm3

493.4±45.0 °C at 760 mmHg

181-183ºC

252.2±28.7 °C

0.0±1.3 mmHg at 25°C

1.673

3.08

1

3

1

24

635

7

CN1C[C@]2([C@@H]3C[C@@H]4[C@]5([C@H]2[C@H]1[C@H]3CO4)C6=CC=CC=C6NC5=O)C=C

NFYYATWFXNPTRM-QJICHLCESA-N

InChI=1S/C20H22N2O2/c1-3-19-10-22(2)16-11-9-24-15(8-13(11)19)20(17(16)19)12-6-4-5-7-14(12)21-18(20)23/h3-7,11,13,15-17H,1,8-10H2,2H3,(H,21,23)/t11-,13+,15+,16+,17-,19-,20-/m0/s1

(1'R,2'S,3S,5'S,6'S,8'R,11'S)-2'-ethenyl-4'-methylspiro[1H-indole-3,7'-9-oxa-4-azatetracyclo[6.3.1.02,6.05,11]dodecane]-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~310.17 mM)
H2O : ~5 mg/mL (~15.51 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)