Astemizol

Astemizol
Nama sistematis (IUPAC)
	1-[(4-fluorofenil)metil]-N-[1-[2-(4-metoksifenil)etil]-4-piperidil]benzoimidazol-2-aminadi
Data klinis
AHFS/Drugs.com	Multum Consumer Information
MedlinePlus	a600034
Kat. kehamilan	C
Status hukum	Ditarik dari perdaran
Rute	Oral
Data farmakokinetik
Ikatan protein	~96%
Metabolisme	Hati (CYP3A4)
Waktu paruh	24 jam
Ekskresi	Feses
Pengenal
Nomor CAS	68844-77-9
Kode ATC	R06AX11
PubChem	CID 2247
Ligan IUPHAR	2603
DrugBank	DB00637
ChemSpider	2160
UNII	7HU6337315
KEGG	D00234
ChEBI	CHEBI:2896
ChEMBL	CHEMBL296419
Data kimia
Rumus	C28H31FN4O
SMILES	eMolecules & PubChem
	InChI InChI=1S/C28H31FN4O/c1-34-25-12-8-21(9-13-25)14-17-32-18-15-24(16-19-32)30-28-31-26-4-2-3-5-27(26)33(28)20-22-6-10-23(29)11-7-22/h2-13,24H,14-20H2,1H3,(H,30,31) ; Key:GXDALQBWZGODGZ-UHFFFAOYSA-N ;

Astemizol (kode pengembangan R43512) adalah obat antihistamin generasi kedua yang memiliki durasi kerja panjang. Astemizol ditemukan oleh Janssen Pharmaceuticals pada tahun 1977. Obat ini ditarik dari pasaran secara global pada tahun 1999 karena efek samping yang jarang terjadi tetapi berpotensi fatal (perpanjangan interval QTc dan aritmia terkait akibat blokade saluran hERG).^[2]^[3]

Farmakologi

Astemizol adalah antagonis reseptor histamin H1. Obat ini memiliki efek antikolinergik dan antipruritik.

Astemizol cepat diserap dari saluran pencernaan dan secara kompetitif mengikat reseptor histamin H1 di saluran pencernaan, rahim, pembuluh darah, dan otot bronkial. Hal ini menekan pembentukan edema dan pruritus (yang disebabkan oleh histamin).

Meskipun beberapa laporan sebelumnya menyatakan bahwa astemizol tidak melewati sawar darah otak, beberapa penelitian^[4]^[5] telah menunjukkan permeabilitas tinggi dan ikatan tinggi pada lipatan protein yang terkait dengan Penyakit Alzheimer.

Astemizol juga dapat bekerja pada reseptor histamin H₃, sehingga menimbulkan efek samping.^{[butuh rujukan]}

Astemizol juga bekerja sebagai FIASMA (penghambat fungsional sfingomielinase asam).^[6]

Astemizol telah diteliti sebagai pengobatan untuk Penyakit Creutzfeldt-Jakob (CJD).^[7]

Toksisitas

Astemizol memiliki LD₅₀ oral sekitar 2052 mg/kg (pada tikus).

Referensi

^ Matsumoto S, Yamazoe Y (February 2001). "Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine". British Journal of Clinical Pharmacology. 51 (2): 133–142. doi:10.1111/j.1365-2125.2001.01292.x. PMC 2014443  . PMID 11259984.
^ Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT (June 1999). "Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole". Journal of Cardiovascular Electrophysiology. 10 (6): 836–843. doi:10.1111/j.1540-8167.1999.tb00264.x. PMID 10376921.
^ Charles O, Onakpoya I, Benipal S, Woods H, Bali A, Aronson JK, et al. (2019). "Withdrawn medicines included in the essential medicines lists of 136 countries". PLOS ONE. 14 (12): e0225429. Bibcode:2019PLoSO..1425429C. doi:10.1371/journal.pone.0225429  . PMC 6887519  . PMID 31791048.
^ Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB (2010). "Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease". Journal of Alzheimer's Disease. IOS Press. 19 (2): 573–589. doi:10.3233/JAD-2010-1262. PMC 2951486  . PMID 20110603.
^ Di L, Kerns EH, Fan K, McConnell OJ, Carter GT (March 2003). "High throughput artificial membrane permeability assay for blood-brain barrier". European Journal of Medicinal Chemistry. 38 (3): 223–232. doi:10.1016/S0223-5234(03)00012-6. PMID 12667689.
^ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, et al. (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8): e23852. Bibcode:2011PLoSO...623852K. doi:10.1371/journal.pone.0023852  . PMC 3166082  . PMID 21909365.
^ Karapetyan YE, Sferrazza GF, Zhou M, Ottenberg G, Spicer T, Chase P, et al. (April 2013). "Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents". Proceedings of the National Academy of Sciences of the United States of America. 110 (17): 7044–7049. Bibcode:2013PNAS..110.7044K. doi:10.1073/pnas.1303510110  . PMC 3637718  . PMID 23576755.

Pranala luar

Statement on Astemizole from Health Canada

[pmid11259984-1] Matsumoto S, Yamazoe Y (February 2001). "Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine". British Journal of Clinical Pharmacology. 51 (2): 133–142. doi:10.1111/j.1365-2125.2001.01292.x. PMC 2014443  . PMID 11259984.

[pmid10376921-2] Zhou Z, Vorperian VR, Gong Q, Zhang S, January CT (June 1999). "Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole". Journal of Cardiovascular Electrophysiology. 10 (6): 836–843. doi:10.1111/j.1540-8167.1999.tb00264.x. PMID 10376921.

[3] Charles O, Onakpoya I, Benipal S, Woods H, Bali A, Aronson JK, et al. (2019). "Withdrawn medicines included in the essential medicines lists of 136 countries". PLOS ONE. 14 (12): e0225429. Bibcode:2019PLoSO..1425429C. doi:10.1371/journal.pone.0225429  . PMC 6887519  . PMID 31791048.

[4] Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB (2010). "Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease". Journal of Alzheimer's Disease. IOS Press. 19 (2): 573–589. doi:10.3233/JAD-2010-1262. PMC 2951486  . PMID 20110603.

[5] Di L, Kerns EH, Fan K, McConnell OJ, Carter GT (March 2003). "High throughput artificial membrane permeability assay for blood-brain barrier". European Journal of Medicinal Chemistry. 38 (3): 223–232. doi:10.1016/S0223-5234(03)00012-6. PMID 12667689.

[pmid18504571-6] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, et al. (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8): e23852. Bibcode:2011PLoSO...623852K. doi:10.1371/journal.pone.0023852  . PMC 3166082  . PMID 21909365.

[7] Karapetyan YE, Sferrazza GF, Zhou M, Ottenberg G, Spicer T, Chase P, et al. (April 2013). "Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents". Proceedings of the National Academy of Sciences of the United States of America. 110 (17): 7044–7049. Bibcode:2013PNAS..110.7044K. doi:10.1073/pnas.1303510110  . PMC 3637718  . PMID 23576755.

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