| description |
Suvorexant (Belsomra® ) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs) and is currently approved for the treatment of insomnia in the United States and Japan. It is a CNS depressant and blocks the binding of wake-promoting neuropeptides orexin A and orexin B to the two orexin receptors (OX1R and OX2R) thus, altering the signaling (action) of orexin in the brain and suppressing the sleep-wake drive.
Suvorexant is a central nervous system (CNS) depressant and can impair daytime wakefulness even when used as prescribed. Prescribers should monitor for somnolence and CNS depressant effects, but impairment can occur in the absence of symptoms, and may not be reliably detected by ordinary clinical exam. CNS depressant effects may persist in some patients for up to several days after discontinuing Suvorexant.
Belsomra (Suvorexant) can impair driving skills and may increase the risk of falling asleep while driving. Discontinue or decrease the dose in patients who drive if daytime somnolence develops. Caution patients taking Belsomra 20 mg against next-day driving and other activities requiring full mental alertness. Caution patients taking lower doses of Belsomra as well, because there is individual variation in sensitivity to Belsomra. |
| Hypnotic drugs |
Suvorexant is a new hypnotic drug developed by the US pharmaceutical giant Merck. Unlike other hypnotics, instead of being administrated on demand like general hypnotics (that is, they are taken only when needed), Merck's Suvorexant is a therapeutic drug, should be subject to long-term administration.
The drug can block Orexins (neuropeptides) to send messages. Orexins (neuropeptides) usually transduces a variety of sobering messages for the human body, being the culprit leading to insomnia.
Professor Andrew Krystal from the Center for Medical Research at Duke University said Merck's drug would become a new drug favored by patients.
Darryle Schoepp, the head of neurology and ophthalmology at Merck, says the drug is especially suitable for patients who have been unable to sleep all night and have received little benefit from existing medications.
“More than 2,000 patients with insomnia that not caused by other medical problems have participated in the two post-trials of Suvorexant,”Said by Merck. The most common side effects of the drug are fatigue and headache.
On August 13, 2014, the US Food and Drug Administration (FDA) approved the release of Belsomra (Suvorexant) from Merck for the treatment of patients who fall asleep and have difficulty sleeping (insomnia). Belsomra is an orexin receptor antagonist and is the first approved drug in this class of drugs. Orexin is a kind of chemical substances that participate into the regulation of sleep wake-up period, playing an important role in maintaining human awakening. Belsomra can alter the information behavior of orexins in the brain.
Figure 1 structure of the Suvorexant. |
| Mechanism of action |
Suvorexant is a dual antagonist of orexin receptors OX1R and OX2R. It exerts its pharmacological effect by inhibiting binding of neuropeptides orexin A and B, also known as hypocretin 1 and 2, that are produced by neurons in the lateral hypothalamus. These neurons control the wake-promoting centers of the brain and are active during wakefulness, especially during motor activities, and stop firing during sleep. By inhibiting the reinforcement of arousal systems, suvorexant use causes a decrease in arousal and wakefulness, rather than having a direct sleep-promoting effect.
References
https://www.drugbank.ca/drugs/DB09034 |
| Clinical evaluation |
The US Food and Drug Administration (FDA) have approved a new remedy for the treatment of insomnia, suvorexant (Belsomra), which is an orexin receptor antagonist.
Suvorexant is the first approved orexin receptor antagonist that inhibits the neuronal activation of the wake-up system by blocking the binding of the neuropeptides, orelectins A and B, to the orexin receptors.
According to suvorexant producer Merck, the FDA recommended its inclusion in the control substance, to which DEA proposed earlier this year that it should be classified as a Category IV control substance under the Controlled Substances law.
At the end of 2012, Merck submitted its listing application to the US Food and Drug Administration (FDA). In May 2013, FDA's Peripheral and CNS Drugs Committee questioned the safety of the initial dose proposed by the company. A few months later, the FDA recommended that the initial dose for most patients should be set at 10 mg.
The company had not prepared the formulation of this dosage, thus have redesigned and produced of several new formulations.
"The FDA has approved four specifications-5, 10, 15, and 20 mg of Belsomra," said by Dr. Ellis Unger who is the director of the FDA's Center for Drug Evaluation and Evaluation. Dr. Unger said in a statement, "using the smallest effective doses can reduce the risk of side effects, such as drowsiness in the morning.”
FDA and Merck said that: it is only needed to administrate 1 tablet of Suvorexant at a time of between half an hour before sleeping every night to at least 7 hours before getting up at least 7 hours, no more than 20 mg per day.
Drowsiness is the most common side effect. In the next day driving behavior study, which was required by the FDA, the capability of the patients who have administrated 20 mg were impaired. The FDA warned that patients subjecting to a 20 mg dosage should be warned not to engage in driving or any other activity requiring vigilance the next day.
The drug may also lead to what the FDA calls "complex behaviors upon sleepy driving and other non-complete arousal state", including cooking and eating, phone calls, or sexual activity. If this behavior occurs, the patient and his family should inform the doctor.
Suvorexant is distributed together with a patient medication guide, which contains detailed safety information.
The FDA said that although three trials were conducted on the drug, none were compared with other approved hypnotic drugs, so the comparative effectiveness of the drug remains unknown.
Information on the indications, dosage and pharmacological effects of new hypnotic drug suvorexant (Belsomra) are edited by Tongtong from the ChemicalBook. |
| side effects |
Suvorexant (BELSOMRA) has possible side effects. Before you begin treatment, it’s important to know what these side effects are and to discuss the risks and benefits of taking BELSOMRA with your doctor.
Below is a list of the most commonly reported adverse events that occurred in 3-month clinical trials:
placebo (n=767) BELSOMRA 15 mg or 20 mg (n=493)
- Diarrhea (placebo 1%, BELSOMRA 2%)
- Dry mouth (placebo 1%, BELSOMRA 2%)
- Upper respiratory tract infection (placebo 1%, BELSOMRA 2%)
- Headache (placebo 6%, BELSOMRA 7%)
- Next-day drowsiness (placebo 3%, BELSOMRA 7%)
- Dizziness (placebo 2%, BELSOMRA 3%)
- Abnormal dreams (placebo 1%, BELSOMRA 2%)
- Cough (placebo 1%, BELSOMRA 2%)
Side effects that you should report to your doctor or health care professional as soon as possible:
- allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
- confusion
- depressed mood
- feeling faint or lightheaded, falls
- hallucinations
- inability to move or speak for up to several minutes while you are going to sleep or waking up
- memory loss
- periods of leg weakness lasting from seconds to a few minutes
- problems with balance, speaking, walking
- restlessness, excitability, or feelings of agitation
- unusual activities while asleep like driving, eating, making phone calls
Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):
- abnormal dreams
- daytime drowsiness
- diarrhea
- dizziness
- headache
|
| Biological activity |
Suvorexant (MK-4305) is a potent OX receptor antagonist, acting on the OX1 receptor and the OX2 receptor with a Ki being 0.55 nM and 0.35 nM, respectively. Phase III. |
| In vivo studies |
In rats, Suvorexant has excellent passive permeability and oral bioavailability, and is conducive to sleep. In addition, suvorexant significantly and dose-dependently decreased the motor activity of rats (10, 30, and 100 mg/kg), dogs (1 and 3 mg/kg), and monkeys (10 mg/kg), while promoting their sleep. |
| Feature |
The regulation of dual OX antagonist on sleep is currently in phase III clinical trials. |
| Definition |
ChEBI: An aromatic amide obtained by formal condensation of the carboxy group of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid with the secondary amino group of 5-chloro-2-[(5R)-5-methyl-1,4-diazepan-1-yl]-1,3-benzoxazole. An rexin receptor antagonist used for the management of insomnia. |
![5-Chloro-2-[(5R)-5-methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl]-1,3-benzoxazole](https://img.chemicalbook.com/ProductImageEN/2018-8/Large/a7488fe0-202f-44b3-8bbc-24f70c3c7f2b.gif)
China
![5-Chloro-2-[(5R)-5-methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl]-1,3-benzoxazole Structure](https://www.chemicalbook.com/CAS/GIF/1030377-33-3.gif)
