Zaleplon

CS-81 · L 846 · Sonata · ZALEPLON · CL-284846 · LJC 10846 · AKOS 92107 · Zaleplon (CRM)

식별자 및 물리적 특성

CAS No.	151319-34-5
분자식	C17H15N5O
평균 분자량	305.33 g/mol
단동위원소 질량	305.12766012 g/mol
SMILES	CCN(C(C)=O)c1cccc(-c2ccnc3c(C#N)cnn23)c1
InChIKey	HUNXMJYCHXQEGX-UHFFFAOYSA-N
PubChem CID	5719
ChEMBL	CHEMBL1521
ChEBI	CHEBI:10102
EC No.	604-794-5
DTXSID	DTXSID5023748

화학 및 물리적 성질

XLogP	1
극성 표면적	74.3
수소 결합 공여자 수	0
수소 결합 수용자 수	4
회전 가능 결합 수	3
무거운 원자 수	23
형식 전하	0
복잡도	487
의약품	DEA NFLIS-Drug Category -> Depressants and TranquilizersDEA Schedule IV Controlled Substance -> DepressantsPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive CompoundsPharmaceuticals -> Hypnotics
LogP(분배 계수)	0.9
용해도	4.03e-02 g/LDMSO: ~20mg/mL
Human Drugs	Breast FeedingLactationMilk, HumanHypnotics and SedativesFDA approved drugs -> Active ingredient
녹는점	157-159 °C157 - 159 °C186-1870C
Physical Description	Solid
Collision Cross Section	173.5 Å² [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]
밀도	1.25±0.1 g/cm3(Predicted)
인화점	9℃
저장 조건	2-8°C
pKa(산도 계수)	-1.47±0.50(Predicted)
물리적 상태	고체
색상	하얀색

화학적 성질

Off-White Powder

안전 및 규제

GHS 분류	WarningH315 (73.6%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P260, P261, P263, P264, P264+P265, P270, P271, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 53 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
규제 정보	DEA schedule IV controlled substance
Hazard Classes and Categories	Skin Irrit. 2 (73.6%)
Treatment	General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. (L1712)
건강 영향	Angina pectoris, bundle branch block, hypertension, hypotension, palpitation, syncope, melena, mouth ulceration, rectal hemorrhage, stomatitis, dysphagia, enteritis, gum hemorrhage, diabetes mellitus, goiter, hypothyroidism, arthrosis, bursitis, hyperesthesia, hyperkinesia, hypotonia, incoordination, insomnia, libido decreased, neuralgia, nystagmus, dry skin, eczema, maculopapular rash, skin hypertrophy, dysuria, hematuria, impotence, kidney calculus, kidney pain, urinary retention, and vaginal hemorrhage (RxList, A308). They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Hepatotoxicity	In multiple premarketing randomized controlled trials, zaleplon was not associated with an increased rate of serum enzyme elevations in comparison to placebo therapy, and no instance of clinically apparent liver injury was reported. Since its approval and widescale use, zaleplon has not been implicated in causing clinically apparent liver disease. Nevertheless, zaleplon is metabolized in the liver by the cytochrome P450 system (predominantly CYP 3A4) and can cause drug-drug interactions, although such interactions appear to be rare. Thus, zaleplon induced liver injury must be rare, if it occurs at all.

용도

개요

Zaleplon was introduced in Sweden and Denmark as a new treatment for insomnia, particularly in patients who have difficulty in falling asleep. Zaleplon is a non-benzodiazepine compound and is the first in a new generation belonging to the pyrazolopyrimidine class, showing therefore fewer benzodiazepine-like side effects. It can be synthesized in 3 steps from the corresponding acetophenone, the key step being the cyclization of the appropriate enaminone with 3-aminopyrazole-4-carbonitrile. Biochemically, Zaleplon is a full agonist at the benzodiazepine o)1 site of the gaba-A receptor complex, but its behavioural profile remains distinct from both benzodiazepine (e.g. Lorazepam) or non-benzodiazepine (e.g. Zopiclone or Zolpidem) sedativehypnotic drugs. Clinical pharmacokinetic analysis showed rapid absorption and elimination. In man, the main metabolic route was oxidative giving the major metabolites 5-oxo Zaleplon and its N-desethyl analog. Both were shown to have no effect at central benzodiazepine receptors and to be rapidly excreted as glucuronides. In patients with chronic insomnia, Zaleplon at 5 and 10 mg/kg significantly reduced sleep latency and improved the quality of sleep compared with placebo without altering the normal sleep architecture. Given its short halflife, the next-day residual effects such as hangover are minimized. It may have some advantages over benzodiazepines regarding unwanted amnesic effects and psychomotor impairment. There was no evidence for the occurrence of rebound insomnia at 10 mg/kg.

용도

Selective non-benzodiazepine GABAA receptor agonist

일반 설명

Zaleplon (Sonata, a pyrazolopyrimidine) isanother short-acting nonbenzodiazepine hypnotic.Pharmacologically and pharmacokinetically, zaleplon is similarto zolpidem; both are hypnotic agents with short halflives.It also has selective high affinity for α1-subunit containingBzRs but produces effects at other BzR/GABAAsubtypes as well. Zaleplon is well absorbed following oraladministration with an absolute bioavailability of approximately30% because of significant presystemic metabolism.It exhibits a mean half-life of approximately 1 hour, with lessthan 1% of the dose excreted unchanged in urine. It is primarilymetabolized by aldehyde oxidase to 5-oxo-zaleplon andis also metabolized to a lesser extent by CYP3A4. Ndemethylationyields desethylzaleplon, which is quickly converted,presumably by aldehyde oxidase, to 5-oxo-desethylzaleplon.These oxidative metabolites are thenconverted to glucuronides and eliminated in urine. All of zaleplon’smetabolites are pharmacologically inactive. It mayhave a more rapid onset (about 1 hour) and termination of actionthan zolpidem, and therefore, it is good to initiate sleepinstead of keeping sleep.