| Revision as of 15:18, 19 January 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (no changed fields - added verified revid - updated 'ChEMBL_Ref') per Chem/Drugbox validation (report errors or [[user talk:CheMoB← Previous edit |
Latest revision as of 19:25, 6 May 2024 edit undoMarbletan (talk | contribs)Extended confirmed users5,416 editsm →The Hydroxyperhexiline:Perhexiline ratio |
| (22 intermediate revisions by 15 users not shown) |
| Line 1: |
Line 1: |
|
|
{{Short description|Chemical compound}} |
| ⚫ |
{{Drugbox| verifiedrevid = 408793116 |
|
|
|
{{Drugbox |
|
| |
|
|
⚫ |
| verifiedrevid = 464199017 |
|
|IUPAC_name = 2-(2,2-dicyclohexylethyl)piperidine |
|
| IUPAC_name = 2-(2,2-dicyclohexylethyl)piperidine |
|
| image=Perhexiline structure.svg |
|
| image = Perhexiline structure.svg |
| ⚫ |
| CASNo_Ref = {{cascite|correct|CAS}} |
|
|
|
<!--Clinical data--> |
|
|
| tradename = |
|
|
| Drugs.com = {{drugs.com|international|perhexiline}} |
|
⚫ |
| pregnancy_category = |
|
⚫ |
| legal_status = |
|
⚫ |
| routes_of_administration = Oral |
|
|
<!--Pharmacokinetic data--> |
|
⚫ |
| bioavailability = Dose Dependent |
|
⚫ |
| metabolism = Saturable Hepatic |
|
⚫ |
| elimination_half-life = Dose Dependent |
|
⚫ |
| excretion = |
|
|
<!--Identifiers--> |
|
⚫ |
| CAS_number_Ref = {{cascite|correct|??}} |
|
⚫ |
| CAS_number = 6621-47-2 |
|
⚫ |
| ATC_prefix = C08 |
|
⚫ |
| ATC_suffix = EX02 |
|
⚫ |
| PubChem = 4746 |
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
⚫ |
| DrugBank = DB01074 |
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| ChemSpiderID = 4584 |
|
| ChemSpiderID = 4584 |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII = KU65374X44 |
|
| UNII = KU65374X44 |
|
⚫ |
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| InChI = 1/C19H35N/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18/h16-20H,1-15H2 |
|
|
⚫ |
| KEGG = D08340 |
|
| InChIKey = CYXKNKQEMFBLER-UHFFFAOYAN |
|
|
|
| ChEBI_Ref = {{ebicite|correct|EBI}} |
| ⚫ |
| smiles = N3C(CC(C1CCCCC1)C2CCCCC2)CCCC3 |
|
|
|
| ChEBI = 35553 |
|
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
|
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
|
| ChEMBL = 75880 |
|
| ChEMBL = 75880 |
|
|
<!--Chemical data--> |
|
⚫ |
| C=19 | H=35 | N=1 |
|
⚫ |
| smiles = N3C(CC(C1CCCCC1)C2CCCCC2)CCCC3 |
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChI = 1S/C19H35N/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18/h16-20H,1-15H2 |
|
| StdInChI = 1S/C19H35N/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18/h16-20H,1-15H2 |
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
| StdInChIKey = CYXKNKQEMFBLER-UHFFFAOYSA-N |
|
| StdInChIKey = CYXKNKQEMFBLER-UHFFFAOYSA-N |
| ⚫ |
| CAS_number=6621-47-2 |
|
| ⚫ |
| ATC_prefix=C08 |
|
| ⚫ |
| ATC_suffix=EX02 |
|
|
| ATC_supplemental= |
|
| ⚫ |
| PubChem=4746 |
|
| ⚫ |
| DrugBank= |
|
| ⚫ |
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| ⚫ |
| KEGG = D08340 |
|
| ⚫ |
| C=19 | H=35 | N=1 |
|
|
| molecular_weight = 277.488 |
|
| ⚫ |
| bioavailability= Dose Dependent |
|
| ⚫ |
| metabolism = Saturable Hepatic |
|
| ⚫ |
| elimination_half-life=Dose Dependent |
|
| ⚫ |
| excretion = |
|
| ⚫ |
| pregnancy_category = |
|
| ⚫ |
| legal_status = |
|
| ⚫ |
| routes_of_administration= Oral |
|
|
}} |
|
}} |
|
|
|
|
'''Perhexiline''' is a prophylactic ] used primarily in ] and ]. Perhexiline is thought to act by inhibiting ]. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O<sub>2</sub> consumption and consequently increases myocardial efficiency. Its clinical use has been limited by its narrow ] and high inter- and intra-individual ] variability. It was outlawed in many countries due to its adverse effects on ]s (PM). The product has been reintroduced for patients who have contraindications, or have not responded to, other treatments for angina. |
|
'''Perhexiline''' ('''Pexsig''') is a prophylactic ] used primarily in ] and ]. Perhexiline is thought to act by inhibiting ]. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O<sub>2</sub> consumption and consequently increases myocardial efficiency. Its clinical use has been limited by its narrow ] and high inter- and intra-individual ] variability. It was outlawed in many countries due to its adverse effects on ]s (PM). The product has been reintroduced for patients who have ]s, or have not responded to other treatments for angina. |
|
|
|
|
|
==Perhexiline metabolism== |
|
==Perhexiline metabolism== |
| Line 41: |
Line 48: |
|
|
|
|
|
==Poor metabolisers== |
|
==Poor metabolisers== |
|
It is estimated that 7–10% of Caucasians are CYP2D6 PMs.<ref name="ref4">Guttendorf, R.J., Wedlund, P.J., Genetic aspects of drug disposition and therapeutics. ''Journal of Clinical Pharmacology''. 32:107–17, (1992).</ref> Most PMs have an ] ] in the CYP2D6 locus which results in the severely compromised metabolism of at least 25 drugs.<ref name="ref5">Gough, A.C., Miles, J.S., Spurr, N.K., ''et al.'' Identification of the primary gene defect at the cytochrome P450 CYP2D locus. ''Nature''. 347(6295):773-6, (1990).</ref> It is believed that there are hundreds of potential polymorphism which will result in a PM, some result in functionally deficient CYP2D6, while others cause the absence of CYP2D6.<ref name="ref6">Kagimoto M, Heim M, Kagimoto K, ''et al.'' Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. '']''. 265(28):17209-14, (1990).</ref><ref name="ref7">Hanioka, N., Kimura, S., Meyer, U.A., ''et al.'' The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934----A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. ''The American Journal of Human Genetics''. 47(6):994-1001, (1990).</ref> |
|
It is estimated that 7–10% of Caucasians are CYP2D6 poor metabolisers (PMs).<ref name="ref4">Guttendorf, R.J., Wedlund, P.J., Genetic aspects of drug disposition and therapeutics. ''Journal of Clinical Pharmacology''. 32:107–17, (1992).</ref> Most PMs have an ] ] in the CYP2D6 locus which results in the severely compromised metabolism of at least 25 drugs.<ref name="ref5">Gough, A.C., Miles, J.S., Spurr, N.K., ''et al.'' Identification of the primary gene defect at the cytochrome P450 CYP2D locus. ''Nature''. 347(6295):773-6, (1990).</ref> It is believed that there are hundreds of potential polymorphism which will result in a PM, some result in functionally deficient CYP2D6, while others cause the absence of CYP2D6.<ref name="ref6">Kagimoto M, Heim M, Kagimoto K, ''et al.'' Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. '']''. 265(28):17209-14, (1990).</ref><ref name="ref7">Hanioka, N., Kimura, S., Meyer, U.A., ''et al.'' The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934----A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. ''The American Journal of Human Genetics''. 47(6):994-1001, (1990).</ref> |
|
|
|
|
|
==The Hydroxyperhexiline:Perhexiline ratio== |
|
== Hydroxyperhexiline:perhexiline ratio== |
|
Cis-hydroxyperhexiline is the primary determinant of perhexiline clearance and there is relatively little interindividual variability in the clearance of Cis-hydroxyperhexiline;<ref name="ref8">Sallustio, B.C., Westley, I.S., and Morris, R.G., Pharmacokinetics of the antianginal agent perhexiline: relationship between metabolic ratio and steady-state dose. ''British Journal of Clinical Pharmacology''. 54:107–14, (2002).</ref> therefore, the Cis-hydroxyperhexiline/perhexiline concentration ratio may be useful for optimizing individual patient treatment with the antianginal agent perhexiline.<ref name="ref8"/> There is a segment of the population with very low hydroxyperhexiline/perhexiline ratios, this subpopulation contains those patients with the PM phenotype.<ref name="ref8"/> It has been suggested that those with ratios ≤0.3 should be considered PMs; thus, providing a simple method for identifying PMs. |
|
Cis-hydroxyperhexiline is the primary determinant of perhexiline clearance and there is relatively little interindividual variability in the clearance of Cis-hydroxyperhexiline;<ref name="ref8">Sallustio, B.C., Westley, I.S., and Morris, R.G., Pharmacokinetics of the antianginal agent perhexiline: relationship between metabolic ratio and steady-state dose. ''British Journal of Clinical Pharmacology''. 54:107–14, (2002).</ref> therefore, the Cis-hydroxyperhexiline/perhexiline concentration ratio may be useful for optimizing individual patient treatment with the antianginal agent perhexiline.<ref name="ref8"/> There is a segment of the population with very low hydroxyperhexiline/perhexiline ratios, this subpopulation contains those patients with the PM phenotype.<ref name="ref8"/> It has been suggested that those with ratios ≤0.3 should be considered PMs; thus, providing a simple method for identifying PMs. |
|
|
|
|
| Line 52: |
Line 59: |
|
|
|
|
|
==References== |
|
==References== |
|
{{reflist|2}} |
|
{{Reflist}} |
|
|
|
|
|
{{Calcium channel blockers}} |
|
{{Calcium channel blockers}} |
|
|
|
|
|
] |
|
] |
|
|
] |
|
|
] |
|
] |
|
] |