Suvorexant is a selective dual antagonist of orexin receptors OX1R and OX2R. It has been approved for the treatment of insomnia. The mechanism by which suvorexant exerts its therapeutic effect in insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

Dexmedetomide (biologically active dextroisomer of medetomidine) is an alpha2-adrenergic agonist which was approved by FDA for the sedation purposes. Upon administration the drug activates the alpha2 receptors thus inhibiting the release of norepinephrine and terminating the propagation of pain signals. Also it inhibits sympathetic activity and thus can decrease blood pressure and heart rate.

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine], a belladonna alkaloid, competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. Scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting (post operative and associated with motion sickness).

Triclofos is primarily indicated in conditions like Insomnia, and can also be given in adjunctive therapy as an alternative drug of choice in Nausea, vertigo, labyrinthine disorders. It is also used sedate people suffering from anxiety or tension before medical investigations. Triclofos is converted to Trichloroethanol in the body .This act on brain and produces sleep. Trichloroethanol decreases time taken to fall asleep and lengthen the sleep. Triclofos is most commonly used agent for sedation in neonates as well as in older infants and children in Japan.

Propiomazine is a typical antipsychotic, blocking H1 receptors and is primarily indicated in conditions Insomnia. Propiomazine was also used under brand name largon for the relief of restlessness and apprehension, preoperatively or during surgery. In addition largon was used as an adjunct to analgesics for the relief of restlessness and apprehension during labor. But this drug was discontinued.

Ethchlorvynol is used to treat insomnia (trouble in sleeping). It developed by Pfizer in the 1950s. In the United States it was sold by Abbott Laboratories under the tradename Placidyl. Although the exact mechanism of action is unknown, ethchlorvynol appears to depress the central nervous system in a manner similar to that of barbiturates – by means of GABA-A receptors modulation. Moderate side effects are: Skin rash or hives; dizziness or faintness; unusual excitement, nervousness, or restlessness. It is addictive and after prolonged use can cause withdrawal symptoms including convulsions, hallucinations, and memory loss.

Meparfynol is a tertiary hexanol and potent tranquilizer with hypnotic/sedative and anticonvulsant effects and exceptionally low therapeutic index. It was discovered by Bayer in 1913 and was used shortly thereafter for the treatment of insomnia, but its use was quickly phased out in response to newer drugs with far more favorable safety profiles. Meparfynol depresses monosynaptic and polysynaptic reflexes and exerted weak ganglion and neuromuscular blocking actions. Meparfynol also produces transitory hypotension, an increase of aortic blood flow. Perfusion of the coronary arteries with Meparfynol led to a slowing of the heart, diminished systolic amplitude, dysrhythmias, and increased coronary flow. Respiration was stimulated with small and depressed with larger doses of Meparfynol.

Carbromal is containing bromide mild hypnotic that has been used to mild insomnia treatment. Carbromal is one of a number of hypnotics containing bromide, which releases the bromide ion on hydrolysis in the body. It has no advantages over other hypnotics. Chronic administration can cause accumulation of bromide ions which have the same distribution as chloride ions but are not actively transported out of cells and are excreted in the urine with a half-life of 10-12 days. Bromism may result from chronic carbromal ingestion and with a plasma bromine concentration of 10-15 mM, the signs are acne, cerebral retardation, cerebellar dysfunction, hyperreflexia, extensor plantar responses, and gastro¬intestinal symptoms. The risk of bromism developing makes carbromal a more dangerous drug than most other hypnotics.

Niaprazine is a potent and selective antagonist of 5-HT2A and alpha-1 adrenergic receptors. It was used for the treatment of sleep disturbances in children and was investigated for the treatment of sleep disorders in patients with attention-deficit hyperactivity disorder and autistic disorder.

Apronalide is an acyclic analog of barbiturates. It was used under tradename "Sedormid" as a sedative an hypnotic agent. In 1934 it was discovered that the drug causes thrombocytopenic purpura. Apronalide is still marketed in Japan, where it is used in combination with caffeine and ibuprofen for the treatment of headache.