Description
Isolated by Ohta from Cocculus diversifolius DC., this alkaloid forms colourless
crystals from MeOH. It is stated to possess a powerful reflex action and to be aspasm stimulant, finally causing paralysis and death in toxic doses. It is also said
to suppress the hypotensive action of dihydroxyphenylethanolethylamine.
Physical properties
Appearance: acicular crystals (crystallized from benzene). Solubility: soluble in
ethanol, acetone, chloroform, and dilute alkali; slightly soluble in water, ether, and
benzene. Melting point: 219–221?°C. Specific optical rotation:?– 71° (c?=?2.1, ethanol). Its hydrochloride, crystallization (water or ethanol), decomposed at 278?°C.?Its
hydroiodide, needle crystal (crystallized from water), decomposed at 272?°C.?Its
picrate, which is yellow needle crystal, decomposed at 176?°C.?Sinomenine is sensitive to light and heat to decompose.
History
The chemical structure of sinomenine is composed of four rings, A, B, C, and D, similar to the structure of morphine. Ring A is a benzene ring, and ring B
is a half-chair-shaped, six-member ring. The C ring is a twisted-chair-type, sixmember ring that has an a, β-unsaturated ketone structure attached to the B ring. The
D ring is a nitrogen-containing, sixmember ring under the B ring. Its structure is
shown below; the current structural modification of sinomenine is mainly focused
on the A/C active group.
Based on the transformation of the A ring, it was found that the 1-substituted
formyl derivative of sinomenine showed the strongest inhibitory effect on the
inflammatory response of the mouse ear. The 4-substituted p-chlorobenzoyl-sinomenine has the strongest anti-inflammatory and analgesic activity. The biotransformation and chemical synthesis were also used to prepare the di-sinomenine
derivatives linked by carbon and carbon, which was stronger than that of sinomenine and had a strong inhibitory effect on cell inflammatory factors. Sinomenine
derivatives of the C ring with a pyrazine ring have a strong inhibitory effect on T, B
lymphocyte proliferation reaction, which can be used for the preparation of immunomodulatory drugs. The transformation of C ring carbonyl yielded a series of shift
alkali derivatives, with strong anti-inflammatory and analgesic effects. These
attempts are important for the development of new drugs.
Uses
weak abortifacient, immunosuppressant, analgesic, antiinflammatory; LD50 (po) 580 mg/kg; (ip) 285 mg/kg(mouse)
Definition
ChEBI: Sinomenine is a morphinane alkaloid.
Indications
It is mainly used for the treatment of rheumatoid arthritis and other types of rheumatism and arrhythmia in clinical.
Biological Activity
Natural anti-inflammatory morphinan analog. Causes degranulation of mast cells in mammalian tissues to release histamine and suppresses production of proinflammatory cytokines. Also displays antinociceptive activity, possibly through activation of the μ -opioid receptor. Stimulates short-term renewal of human embryonic stem cells (ESCs) in vitro .
Pharmacology
Sinomenine has anti-inflammatory, immunosuppressive, analgesic sedation, antiarrhythmic, detoxification, and other pharmacological effects, while the half-life of
sinomenine is short. In addition, sinomenine also causes a strong histamine release,
which leads to rash, gastrointestinal reactions, and other side effects, limiting its
wide range of clinical applications.
1. Effects on central nervous system
(a) Analgesic effect: The chemical structure of sinomenine and morphine are similar (Fig.?3). They both act on the central nervous system with a significant analgesic effect, but the mechanisms are different. It has been shown that the
analgesic effect of sinomenine has nothing to do with the release of histamine.
(b) Sedative effect: Sinomenine has an inhibitory effect on the central nervous system. The sedative effect works by inhibiting the excitement of advanced neurological activity. Sinomenine can also eliminate the “anger” response of mice
caused by electrical stimulation, showing a stabilizing effect. In addition,
although, like morphine, it had mainly a sedative effect on the central nervous
system, sinomenine also has some excitatory effects on some parts of the central nervous system, especially the spinal cord.
Other effects on the central nervous system: Sinomenine may, to a slight degree,
induce vomiting. Sinomenine also has local anesthetic effects on frog nerve
endings and rabbit cornea that could be applied for local infiltration
anesthesia.
2. Effects on peripheral nervous system
Sinomenine can reversibly block the neuromuscular transmission, which showed
a concentration-dependent inhibitory effect. Sinomenine had no significant effect
on nerve stem excitability and conductivity.
3. Impact on cardiovascular system
Sinomenine has a significant antihypertensive effect. Sinomenine also has a significant antagonistic effect on ischemic arrhythmia.
4. Anti-inflammatory and antiallergic effects
The anti-inflammatory effect of sinomenine is significant.
Clinical Use
The treatment of rheumatism and rheumatoid arthritis is one of the most important
clinical applications of sinomenine. Sinomenine is particularly suitable for the treatment of arrhythmia caused by organic heart disease. Sinomenine is used for the
treatment of glomerular disease, which can reduce urinary protein and relieve
hematuria symptoms, and the side effects were significantly lower than that of
tripterygium glycoside tablets, which are commonly used in clinical practice. In
addition, sinomenine can significantly inhibit renal interstitial fibrosis and the production of tissue growth and growth factor TGF-β1. Sinomenine can significantly
delay the development of chronic renal failure and effectively treat ankylosing
spondylitis.
Purification Methods
Crystallise the salt from water (1g/1.5mL) or EtOH. The free base [115-53-7] M 329.4, has m 161o (from EtOH) (and again at 182o) after crystallisation from *C6H6, and [] D -78.9o (c 1, EtOH). The picrate has m 159-162o(dec) (from H2O). [Beilstein 21 II 470, 21 III/IV 6670.]
References
Ohta., Ber. ges. Physiol., 33, 352 (1925)
Ohta, Kitasato., Arch. expo Med., 6, 259, 283 (1925)
Raymond-Hamet., Compt. rend. Soc. Biol., 125, 509 (1937)
