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Nalmefene |
17-cyclopropylmethyl-4,5α-epoxy-6-methylenemorphinan-3,14-diol |
Sihuan Pharmaceutical Holdings Group Ltd a leading pharmaceutical company with the largest cardio-cerebral vascular drug franchise in China’s prescription market, announced that the new Category 3.1 drug, the Nalmefene Hydrochloride Injection received a new drug certificate (H20120078) and approval for production (2012S00818) from the State Food and Drug Administration. Nalmefene Hydrochloride is yet another generic drug for which the Company has received approval for production following the Roxatidine Acetate Hydrochloridefor Injection. It will be manufactured by Beijing Sihuan Pharmaceutical Co., Ltd., a wholly-owned manufacturing subsidiary of the Company.
Nalmefene hydrochloride is a next generation opioid (opium) receptor inhibitor following Naloxone and Naltrexone. The injection formulation of Naloxone hydrochloride was invented by Ohmeda Pharmaceuticals and was approved by the US Food and Drug Administration (FDA) in 1995. The clinical uses of Nalmefene hydrochloride include anti-shock, neuroprotection, treatment for acute morphine poisoning, drug relapse prevention, recovery from the after-effects of anesthesia such as respiratory and nerve center depression and the treatment of unconsciousness persons.
The drug is also effective for treating heart failure and spinal cord injuries, for cerebral protection, etc. Multi-centre, randomized, blind, and positive-controlled clinical research of Nalmefene hydrochloride of Sihuan Pharmaceutical were performed by the Peking University First Hospital, the First Affiliated Hospital of China Medical University, Xijing Hospital (The First Affiliated Hospital of the Fourth Military Medical College) and Qingdao Municipal Hospital.
Compared to Naloxone, Nalmefene demonstrates longer curative effects and fewer adverse reactions. With its high bioavailability, biological activities and biofilm penetration ability, it helps to regulate respiration, circulation, digestion, and the endocrine and nervous systems. It is becoming a substitute for Naloxone, and has been included in Part B of the National Medicine Catalogue. At present, the size of the Nalmefene hydrochloride market in China is approximately RMB1 billion. As a substitution for Naloxone hydrochloride, Nalmefene hydrochloride has enormous market potential.
Diseases of the central nervous system (CNS) are common in China, which has an immense patient base. Due to the rapid pace of modern life, accelerated urbanisation and mental stress, the demand for CNS medicines has seen rapid growth in recent years given the rising number of patients. According to IMS, the size of the CNS drug market now exceeds RMB 23 billion. With the CNS drug market expected to reach RMB 100 billion in 2020, the Group sees great potential and strong growth prospects in the market.Dr. Che Fengsheng, Chairman and CEO of Sihuan Pharmaceutical, said, “Nalmefene Hydrochloride has shown better characteristics for treatment and higher clinical value than Naloxone. Its market demonstrates great potential to expand. Leveraging Sihuan Pharmaceutical’s strong marketing capabilities and extensive sales and distribution network, we believe that our market share for Nalmefene Hydrochloride will see rapid growth, which will strengthen our position in drugs for the treatment of major diseases of the central nervous system. Together with other new products, this will in turn enhance the continuous development and growth of Sihuan Pharmaceutical in China’s prescription drug market and create value for the shareholders and the Company.”
REVEX (nalmefene hydrochloride injection), an opioid antagonist, is a 6-methylene analogue of naltrexone. The chemical structure is shown below:
Molecular Formula: C21H25NO3•HCl
Molecular Weight: 375.9, CAS # 58895-64-0
Chemical Name: 17-(Cyclopropylmethyl)-4,5a-epoxy-6-methylenemorphinan-3,14-diol, hydrochloride salt.
Nalmefene hydrochloride is a white to off-white crystalline powder which is freely soluble in water up to 130 mg/mL and slightly soluble in chloroform up to 0.13 mg/mL, with a pKa of 7.6.
REVEX is available as a sterile solution for intravenous, intramuscular, and subcutaneous administration in two concentrations, containing 100 µg or 1.0 mg of nalmefene free base per mL. The 100 µg/mL concentration contains 110.8 µg of nalmefene hydrochloride and the 1.0 mg/mL concentration contains 1.108 mg of nalmefene hydrochloride per mL. Both concentrations contain 9.0 mg of sodium chloride per mL and the pH is adjusted to 3.9 with hydrochloric acid.
Concentrations and dosages of REVEX are expressed as the free base equivalent of nalmefene.
Nalmefene (Revex), originally known as nalmetrene, is an opioid receptor antagonistdeveloped in the early 1970s,[1] and used primarily in the management of alcoholdependence, and also has been investigated for the treatment of other addictions such aspathological gambling and addiction to shopping.
Nalmefene is an opiate derivative similar in both structure and activity to the opiate antagonist naltrexone. Advantages of nalmefene relative to naltrexone include longer half-life, greater oral bioavailability and no observed dose-dependent liver toxicity. As with other drugs of this type, nalmefene can precipitate acute withdrawal symptoms in patients who are dependent on opioid drugs, or more rarely when used post-operatively to counteract the effects of strong opioids used in surgery.
Nalmefene differs from naltrexone by substitution of the ketone group at the 6-position of naltrexone with a methylene (CH2) group, which considerably increases binding affinity to the μ-opioid receptor. Nalmefene also has high affinity for the other opioid receptors, and is known as a “universal antagonist” for its ability to block all three.
- US patent 3814768, Jack Fishman et al, “6-METHYLENE-6-DESOXY DIHYDRO MORPHINE AND CODEINE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS”, published 1971-11-26, issued 1974-06-04
- Barbara J. Mason, Fernando R. Salvato, Lauren D. Williams, Eva C. Ritvo, Robert B. Cutler (August 1999). “A Double-blind, Placebo-Controlled Study of Oral Nalmefene for Alcohol Dependence”. Arch Gen Psychiatry 56 (8): 719.
- Clinical Trial Of Nalmefene In The Treatment Of Pathological Gambling
- http://www.fda.gov/cder/foi/label/2000/20459S2lbl.pdf
- “Efficacy of Nalmefene in Patients With Alcohol Dependence (ESENSE1)”.
- “Lundbeck submits Selincro in EU; Novo Nordisk files Degludec in Japan”. thepharmaletter. 22 December 2011.
- Nalmefene Hydrochloride Drug Information, Professional
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