Products
Orexin receptor antagonists are commercially available in tablet form. The first agent in this group to be approved in the United States was suvorexant (Belsomra) in 2014. Lemborexant (Dayvigo) followed in 2019.
Structure and properties
Orexin receptor antagonists are characterized by a central ring structure to which heterocycles are attached on both sides.
Effects
Orexin receptor antagonists have sleep-promoting and depressant properties. They are antagonists at the orexin receptors OX1R and OX2R. These are G-protein coupled receptors (GPCRs). The drugs block the binding of the neuropeptides orexin A and orexin B, which are produced exclusively in the hypothalamus of nerve cells. These peptide neurotransmitters are involved in promoting and maintaining wakefulness. They also play a role in food intake. The term comes from Latin and means appetite. The orexins are peptides with a sequence homology of only 46%. Orexin A consists of 33 amino acids and orexin B consists of 28 amino acids. They are also called hypocretins. Within the drug group, SORA and DORA are distinguished:
- SORA: Selective orexin receptor antagonists bind only one of the two OX receptors.
- DORA: Dual orexin receptor antagonists bind to both OX receptors.
The agents available to date are dual antagonists. The mechanism of action differs from benzodiazepines and Z-drugs such as zolpidem, which interact with the GABA-A receptor.
Indications
For the treatment of sleep onset and sleep maintenance disorders.
Dosage
According to the professional information. Tablets are taken immediately before bedtime and no more than once per night. When administered with a meal, the onset of action is delayed.
Active ingredients
Active ingredients with a marketing authorization:
- Lemborexant (Dayvigo).
- Suvorexant (Belsomra) – 1. representative
Not in trade:
- Filorexant
- SB-649868
- The development of almorexant has been discontinued.
Abuse
According to the studies conducted, like other sleep aids, the active ingredients have a potential for abuse as depressant intoxicants.
Contraindications
Contraindications include:
- Hypersensitivity
- Narcolepsy
Full precautions can be found in the drug label.
Interactions
The orexin receptor antagonists are substrates of CYP450 isoenzymes and corresponding interactions with inhibitors and inducers are possible. Combination with alcohol and centrally depressant drugs is not recommended because adverse effects may be increased.
Adverse effects
The most common potential adverse effect is drowsiness the following day, which may adversely affect responsiveness. One cause is the relatively long half-life of the active ingredients. The development of dependence has not been observed in the corresponding studies so far. This is an advantage over many other sleep aids. Orexin receptor antagonists could even be suitable for addiction therapy, according to various studies.
