User:Wickypears/sandbox

Small Changes

-add picture of how rimantadine is synthesized

-create link to Flumadine (rimantadine-HCl) and then link that back to rimantadine. Include picture of what flumadine actually looks like: (will draw using Chem-draw)

• Flumadine

-the IUPAC name listed under rimantadine is incorrect. It should be: 1-(1-adamantyl)ethanamine ⁷

Main Section

• Change the sentence "When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza." to "When taken in the first 48 hours of symptoms, Rimantadine can shorten the duration of and mitigate symptoms including fever⁸."

• (After the sentence: Both rimantadine and the similar drug amantadine are derivates of adamantane:) Rimantadine is found to be more effective than amantadine because it has fewer symptoms than amantadine¹¹.

• Change "100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to rimantadine" to "Seasonal H3N2, the 2009 pandemic flu and other mutation samples tested have shown resistance to" rimantadine..."

Synthesis

Rimantadine Synthesis as synthesized in Europe.

1-carboxyadamatanones are reduced with sodium borohydride to create racemic hydroxy acid. Excess methyllithium is then added to create methyl ketones which when reduced with lithium aluminum hydride gives the amine group ([11] in the references).

The synthesis pictured to the right is a synthesis of rimantadine in Europe, listed here.

Drug Interactions

Taking anticholigenic drugs with amantadine may increase underlying seizure disorders and aggravate congestive heart failure^[8].

Side Effects

Add:

• trouble sleeping (insomnia)
• confusion
• anxiety

(Rimantadine shows less CNS symptoms than its sister drug Amantadine^[8].)

Medical Use

Influenza A

(Before the first setence): Rimantadine inhibits influenza activity by binding to amino acids in the M2 transmembrane channel and blocking proton transport across the M2 channel¹⁰. (After capsid): The M2 channel is known to be responsible for viral replication in the influenza virus. (After last sentence). Rimantadine is bound inside the pore to amantadane specific amino acid binding sites with hydrogen bonding and van der Waals interactions. The ammonium group (with neighboring water molecules) is positioned towards the C terminus while the amantadane group is positioned towards the N-terminus when bound inside the M2 pore. The M2 channel pictured to the right, shows an amino acid mutation in the M2 channel affects rimantadine binding to the M2 channel.

RImantadine Enantiomers Interactions with M2

Rimantadine when sold as flumadine is always present as a racemic mixture, which means that both the R and S state are present in the drug. Solid state NMR studies have shown that the R enantiomer has a stronger binding affinity to the M2 channel pore than the S-enantiomer of rimantadine. Antiviral assay and electrophysiology studies show that there is no significant difference between the R and S enantiomers in binding affinity to amino acids in the M2 channel. Since the enantiomers have similar binding affinity, they also have similar ability to block the channel pore and work as an effective antiviral.

Rimantadine binding into lumenal (top) or peripheral (bottom) binding sites with influenza M2 channel Serine 31 (gold) or Asparagine 31 (blue).

Parkinson's Disease

• just put the paragraph from the wiki article here

Other

*Rimantadine is shown to be affective against other RNA-containing viruses. It can treat arboviruses like Saint Louis ecephalitis and Sindbis. Other viruses that can be treated with Rimantadine include  respiratory synctial and parainfluenza viruses[6].

• Rimantadine has also been shown to treat chronic hepatitis C ^[9].

Synonyms

1-(1-Adamantyl)ethanamine

1-(Adamantan-1-yl)ethanamine

1-(adamantan-1-yl)ethan-1-amine

alpha-Methyl-1-adamantanemethylamine

alpha-Methyladamantanemethylamine

Rimantadine [INN:BAN]

Rimantadinum [INN-Latin]

1-(1-Adamantyl)ethylamin

Remantadine

Rimantadina [INN-Spanish]

1-Adamantan-1-yl-ethylamine

RIMANTADIN

HSDB 7438

CHEMBL959

BRN 2715740

1-Adamantanemethylamine, .alpha.-methyl-

.alpha.-Methyladamantanemethylamine

1-(1-adamantyl)-ethylamine

1-(tricyclo[3.3.1.1~3,7~]dec-1-yl)ethanamine

Riamantadine

Rimantadina

Rimantadinum

Tricyclo(3.3.1.13,7)decane-1-methanamine, alpha-methyl-

[1-(1-adamantyl)ethyl]amine hydrochloride

Tricyclo(3.3.1.1(sup 3,7))decane-1-methanamine, alpha-methyl-

1-ADAMANTANEMETHYLAMINE, alpha-METHYL-

1-Rimantadine

887336-05-2

Tricyclo[3.3.1.13,7]decane-1-methanamine, a-methyl-

Rimant

1-(1-adamantyl)ethylamine

Rimantadine (INN)

Enamine_005755

NCGC00159491-02

Rimant & .alpha. IFN

Rimantadine (Flumadine)

Rimantidine & .alpha.IFN

1-Adamantan-1-ylethylamine

rimantidin

Rimantadin A

(R)-1-(Adamantan-1-yl)ethan-1-amine

1-adamantanylethylamine

Maybridge1_002066

SCHEMBL2981

1-tricyclo[3.3.1.1~3,7~]dec-1-ylethanamine

Oprea1_602732

SCHEMBL2619249

CHEMBL1201272

DTXSID2023561

SCHEMBL20409367

CHEBI:94440

CTK6A4437

HMS1410F13

HMS2090L19

HMS3604N13

HMS3655J05

1-Adamantanemethylamine, ?-methyl-

ALBB-013870

BCP12269

HY-B0338

ZX-AN012619

ANW-72018

BBL013215

BDBM50216627

MFCD00869344

s1964

STK177253

(alpha-methyl-1-adamantyl)methylamine

AKOS000264537

AKOS006238592

AKOS016038537

.alpha.-Methyl-1-adamantanemethylamine

AM84461

API0024288

BBV-156986

CCG-236078

CS-2380

DB00478

FCH3207896

MCULE-9027470290

IDI1_007990

NCGC00159491-03

NCGC00159491-05

AK-58175

AS-68744

CC-34261

LS-15019

OR315791

SBI-0206810.P001

AB0012750

AX8049536

DB-042207

FT-0630403

H6325

ST45025920

SW220023-1

EN300-33990

C07236

D08483

Q42171

1-[(3R,5S,7s)-adamantan-1-yl]ethan-1-amine

AB00638368-09

AB00959689-03

AB01506092_02

AB01506092_03

392R284

C-06592

BRD-A84282119-003-01-2

Z56757137

1-(Tricyclo[3.3.1.1>3,7>]dec-1-yl)ethanamine (HCl)

Tricyclo(3.3.1.1^3,7)decane-1-methanamine, .alpha.-methyl-

1-(1-Adamantyl)ethylamine Hydrochloride;Rimantadine hydrochloride

Tricyclo(3.3.1.1(sup 3,7))decane-1-methanamine, .alpha.-methyl-

Tricyclo[3,3,1,1(3,7)]decane-1-methanamine, .alpha.-methyl-

Tricyclo(3.3.1.1^3,7)decane-1-methanamine, .alpha.-methyl- & IFN.alpha

References

[1] Evidente, VGH, et al. "A Pilot Study on the Motor Effects of Rimantadine in Parkinson's Disease." Clinical Neuropharmacology, vol. 22, no. 1, 1999, pp. 30-32.

[2] Galvao, M. G. A., Santos, M. A. Rocha Crispino, and da Cunha, A. J. L. Alves. "Amantadine and Rimantadine for Influenza A in Children and the Elderly." Cochrane Database of Systematic Reviews, no. 1, 2008, pp. CD002745, doi:10.1002/14651858.CD002745.pub2.

[3]Jefferson, T., et al. "Amantadine and Rimantadine for Influenza A in Adults." Cochrane Database of Systematic Reviews, no. 2, 2006, pp. CD001169.pub3, doi:10.1002/14651858.CD001136.pub3.

[4] WEINTRAUB, M., and P. EVANS. "Rimantadine - a New Agent for the Prophylaxis and Treatment of Influenza-A." Hospital Formulary, vol. 21, no. 4, 1986, pp. 431-&.

[5] WINTERMEYER, S. M., and M. C. NAHATA. "Rimantadine - a Clinical Perspective." Annals of Pharmacotherapy, vol. 29, no. 3, 1995, pp. 299-310, doi:10.1177/106002809502900312.

[6] ZLYDNIKOV, D. M., et al. "Study of Rimantadine in the Ussr - a Review of the Literature." Reviews of Infectious Diseases, vol. 3, no. 3, 1981, pp. 408-421.

[7] National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 5071, Rimantadine. Retrieved November 14, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/Rimantadine.

[8] Zimmerman, Richard Kent, et al. "Influenza, influenza vaccine, and amantadine/rimantadine." Journal of Family Practice, vol. 45, no. 2, Aug. 1997, p. 107+. Gale Academic OneFile,

[9] Younossi ZM, Perrillo RP. The roles of amantadine, rimantadine, ursodeoxycholic acid, and NSAIDs, alone or in combination with alpha interferons, in the treatment of chronic hepatitis C. Semin Liver Dis. 1999;19 Suppl 1:95-102. PMID: 10349697.

[10] Moorthy NS, Poongavanam V, Pratheepa V. Viral M2 ion channel protein: a promising target for anti-influenza drug discovery. Mini Rev Med Chem. 2014;14(10):819-30. PMID: 25342196.

[11] Jefferson, T., Demicheli, V., Di Pietrantonj, C., & Rivetti, D. (2006). Amantadine and rimantadine for influenza A in adults. The Cochrane database of systematic reviews, 2006(2), CD001169. https://doi.org/10.1002/14651858.CD001169.pub3

[12] Percy S. Manchand, Richard L. Cerruti, Joseph A. Martin, Christopher H. Hill, John H. Merrett, Elizabeth Keech, Robert B. Belshe, Edward V. Connell, and Iain S. Sim

1990 33 (7), 1992-1995 DOI: 10.1021/jm00169a029