Synonym
Methenamine mandelate; Hexydaline; Mandacon
IUPAC/Chemical Name
1,3,5,7-Tetraazatricyclo(3.3.1.1(3,7))decane, mono(alpha-hydroxybenzeneacetate)
InChi Key
UXNFIJPHRQEWRQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C8H8O3.C6H12N4/c9-7(8(10)11)6-4-2-1-3-5-6;1-7-2-9-4-8(1)5-10(3-7)6-9/h1-5,7,9H,(H,10,11);1-6H2
SMILES Code
O=C(O)C(O)C1=CC=CC=C1.N2(C3)CN4CN3CN(C4)C2
Purity
>95% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
Biological target:
Methenamine mandelate-loaded nanoparticle induces DNA damage and apoptosis of cancer cells.
In vitro activity:
At pH 5.5, concentrations of 32 to 125 mg hexamine per 1 caused some inhibition of bacterial growth, but 250 to 500 mg/l were needed to suppress growth overnight.
Reference: Infection. 1981;9(5):223-7. https://pubmed.ncbi.nlm.nih.gov/7028634/
In vivo activity:
In the aged mice model, there was a decreased urothelial permeability (as seen by retention of fluorescein isothiocyanate-conjugated-dextran fluorescence in superficial cells) and increased urinary IgA in mice treated with MH (methenamine hippurate) compared with controls.
Reference: Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e205-e210. https://pubmed.ncbi.nlm.nih.gov/35536668/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
292.34
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Greenwood D, Slack RC. The antibacterial activity of hexamine (methenamine), hexamine hippurate and hexamine mandelate. Infection. 1981;9(5):223-7. doi: 10.1007/BF01640720. PMID: 7028634.
2. Musher DM, Griffith DP, Tyler M, Woelfel A. Potentiation of the antibacterial effect of methenamine by acetohydroxamic acid. Antimicrob Agents Chemother. 1974 Feb;5(2):101-5. doi: 10.1128/AAC.5.2.101. PMID: 4840424; PMCID: PMC428928.
3. Sawhill JL, Mora A, McDaniel K, Ligon MM, Lowder JL, Mysorekar IU, Chu CM. The Impact of Methenamine Hippurate Treatment on Urothelial Integrity and Bladder Inflammation in Aged Female Mice and Women With Urinary Tract Infections. Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e205-e210. doi: 10.1097/SPV.0000000000001185. Epub 2022 Apr 28. PMID: 35536668; PMCID: PMC9232912.
4. Tavakkoli H, Imani M, Seyyed MR, Rezvani M. The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods. Int J Reprod Biomed. 2020 Aug 19;18(8):579-590. doi: 10.18502/ijrm.v13i8.7497. PMID: 32923925; PMCID: PMC7457151.
In vitro protocol:
1. Greenwood D, Slack RC. The antibacterial activity of hexamine (methenamine), hexamine hippurate and hexamine mandelate. Infection. 1981;9(5):223-7. doi: 10.1007/BF01640720. PMID: 7028634.
2. Musher DM, Griffith DP, Tyler M, Woelfel A. Potentiation of the antibacterial effect of methenamine by acetohydroxamic acid. Antimicrob Agents Chemother. 1974 Feb;5(2):101-5. doi: 10.1128/AAC.5.2.101. PMID: 4840424; PMCID: PMC428928.
In vivo protocol:
1. Sawhill JL, Mora A, McDaniel K, Ligon MM, Lowder JL, Mysorekar IU, Chu CM. The Impact of Methenamine Hippurate Treatment on Urothelial Integrity and Bladder Inflammation in Aged Female Mice and Women With Urinary Tract Infections. Female Pelvic Med Reconstr Surg. 2022 Jun 1;28(6):e205-e210. doi: 10.1097/SPV.0000000000001185. Epub 2022 Apr 28. PMID: 35536668; PMCID: PMC9232912.
2. Tavakkoli H, Imani M, Seyyed MR, Rezvani M. The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods. Int J Reprod Biomed. 2020 Aug 19;18(8):579-590. doi: 10.18502/ijrm.v13i8.7497. PMID: 32923925; PMCID: PMC7457151.
1: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. Methenamine Mandelate. 2021 Jan 18. PMID: 30000080.
2: Zhang L, Hao W, Xu L, Gao Y, Wang X, Zhu D, Chen Z, Zhang X, Chen H, Mei L. A pH-sensitive methenamine mandelate-loaded nanoparticle induces DNA damage and apoptosis of cancer cells. Acta Biomater. 2017 Oct 15;62:246-256. doi: 10.1016/j.actbio.2017.08.019. Epub 2017 Aug 16. PMID: 28822844.
3: Pavitrapok C, Williams DA. Determination of methenamine, methenamine mandelate and methenamine hippurate in pharmaceutical preparations using ion- exchange HPLC. J Pharm Biomed Anal. 2006 Mar 18;40(5):1243-8. doi: 10.1016/j.jpba.2005.09.017. Epub 2005 Nov 17. PMID: 16298099.
4: Jeantet A, Thea A, Ferrando U, Gaido M, Rotunno M, Martini PF, Vercellone A. Infectious nephrolithiasis: results of treatment with methenamine mandelate. Contrib Nephrol. 1987;58:233-5. doi: 10.1159/000414526. PMID: 3691135.
5: Kevorkian CG, Merritt JL, Ilstrup DM. Methenamine mandelate with acidification: an effective urinary antiseptic in patients with neurogenic bladder. Mayo Clin Proc. 1984 Aug;59(8):523-9. doi: 10.1016/s0025-6196(12)61489-x. PMID: 6379319.
6: Lamid S. Ascorbic acid and methenamine mandelate on the urinary pH of spinal cord injury patients. J Urol. 1983 Apr;129(4):845-6. doi: 10.1016/s0022-5347(17)52396-4. PMID: 6842722.
7: Roesel RA, Coryell ME, Blankenship PR, Thevaos TG, Hall WK. Interference by methenamine mandelate in screening for organic and amino acid disorders. Clin Chim Acta. 1980 Jan 1;100(1):55-8. doi: 10.1016/0009-8981(80)90185-0. PMID: 7351078.
8: Gabrielson RM. Rational use of methenamine mandelate. Am J Hosp Pharm. 1979 Dec;36(12):1658-9. PMID: 525640.
9: Gleckman R, Alvarez S, Joubert DW, Matthews SJ. Drug therapy reviews: methenamine mandelate and methenamine hippurate. Am J Hosp Pharm. 1979 Nov;36(11):1509-12. PMID: 391033.
10: Pearman JW, Peterson GJ, Nash JB. The antimicrobial activity of urine of paraplegic patients receiving methenamine mandelate. Invest Urol. 1978 Sep;16(2):91-8. PMID: 30734.
11: Furuya E. Removal of interference by erythromycin, phenazopyridine, and methenamine mandelate in the Porter-Silber reaction. Clin Chem. 1977 Nov;23(11):2136-8. PMID: 912880.
12: Keswani RK, Chugh TD, Hooda RS, Beniwal JS. Prevention of recurrent urinary tract infection with methenamine mandelate. Indian J Med Res. 1976 Aug;64(8):1168-72. PMID: 992846.
13: Timmerman RJ, Schroer JA. Lipoid pneumonia caused by methenamine mandelate suspension. JAMA. 1973 Sep 17;225(12):1524-5. PMID: 4740722.
14: Turczan JW, Goldwitz BA. Nuclear magnetic resonance analysis of pharmaceuticals. IX. Methenamine and methenamine mandelate in tablets. J Assoc Off Anal Chem. 1973 May;56(3):669-73. PMID: 4779904.
15: Dow ML. Semiautomated colorimetric determination of methenamine and methenamine mandelate in tablets. J Assoc Off Anal Chem. 1973 May;56(3):647-52. PMID: 4779900.
16: Daly RE, Chafetz L. Semiautomated determination of mandelic acid as benzaldehyde in content uniformity testing of methenamine mandelate tablets. J Pharm Sci. 1973 May;62(5):816-7. doi: 10.1002/jps.2600620526. PMID: 4705693.
17: Chen TM, Chafetz L. Selective determination of free urinary formaldehyde after oral dosage with methenamine mandelate. Invest Urol. 1972 Nov;10(3):212-4. PMID: 4640491.
18: Joseph JI, Joshi W, Joshi AM. Hypersensitivity to methenamine mandelate. J Med Soc N J. 1971 Dec;68(12):983-5. PMID: 5289077.
19: Taylor PH, Galuto P, Naille R, Heydinger DK, Bowers JD. Experimental use of methenamine mandelate in treatment of burn wounds in rats. J Trauma. 1970 Apr;10(4):331-3. doi: 10.1097/00005373-197004000-00006. PMID: 5435844.
20: Ross RR Jr, Conway GF. Hemorrhagic cystitis following accidental overdose of methenamine mandelate. Am J Dis Child. 1970 Jan;119(1):86-7. doi: 10.1001/archpedi.1970.02100050088021. PMID: 5410299.
