Adapromine Explained

Adapromine is an antiviral drug of the adamantane group related to amantadine (1-aminoadamantane), rimantadine (1-(1-aminoethyl)adamantane), and memantine (1-amino-3,5-dimethyladamantane) that is marketed in Russia for the treatment and prevention of influenza.[1] [2] [3] [4] It is an alkyl analogue of rimantadine and is similar to rimantadine in its antiviral activity but possesses a broader spectrum of action, being effective against influenza viruses of both type A and B.[5] Strains of type A influenza virus with resistance to adapromine and rimantadine and the related drug deitiforine were encountered in Mongolia and the Soviet Union in the 1980s.[6] [7]

Electroencephalography (EEG) studies of animals suggest that adapromine and related adamantanes including amantadine, bromantane (1-amino-2-bromophenyladamantane), and memantine have psychostimulant-like and possibly antidepressant-like effects, and that these effects may be mediated via catecholaminergic processes.[8] [9] [10] [11] These psychostimulant effects differ qualitatively from those of conventional psychostimulants like amphetamine however, and the adamantane derivatives have been described contrarily as "adaptogens" and as "actoprotectors".[12]

In 2004, it was discovered that amantadine and memantine bind to and act as agonists of the σ1 receptor (Ki = 7.44 μM and 2.60 μM, respectively) and that activation of the σ1 receptor is involved in the dopaminergic effects of amantadine at therapeutically relevant concentrations.[13] These findings might also extend to the other adamantanes such as adapromine, rimantadine, and bromantane and could explain the psychostimulant-like effects of this family of compounds.

Synthesis

The first synthesis of adapromine was disclosed in patents by DuPont published in 1967.[14]

1-Adamantanecarboxylic acid, as its acid chloride, is treated with a cadmium-modified Grignard reagent, which gives the ketone (6). Oxime formation with hydroxylamine, followed by reduction using lithium aluminium hydride yields adapromine.[14] [15]

See also

Notes and References

  1. Spasov AA, Khamidova TV, Bugaeva LI, Morozov IS . Adamantane derivatives: Pharmacological and toxicological properties (review). Pharmaceutical Chemistry Journal. 34. 1. 2000. 1–7. 0091-150X. 10.1007/BF02524549. 41620120.
  2. Lavrova LN, Indulen MK, Ryazantseva GM, Korytnyi VS, Yashunskii VG . Synthesis and biological activity of some 1-hydroxy-3-aminoalkyladamantanes and their derivatives. Pharmaceutical Chemistry Journal. 24. 1. 1990. 35–39. 0091-150X. 10.1007/BF00769383. 8544357.
  3. Gavrilova NA, Frolenko TA, Semichenko ES, Suboch GA . Synthesis of naphtho[1,2-d]imidazoles containing an adamantyl fragment. Russian Journal of Organic Chemistry. 46. 5. 2010. 777–778. 1070-4280. 10.1134/S1070428010050349. 94469430.
  4. Rodionov VN, Sklyarova AS, Shamota TV, Schreiner PR, Fokin AA . Selective reductive dimerization of homocubane series oximes. Russian Journal of Organic Chemistry. 47. 11. 2011. 1695–1702. 1070-4280. 10.1134/S1070428011110078. 94472143.
  5. Leneva IA, Glushkov RG, Gus'kova TA . Drugs for chemotherapy and prophylaxis of influenza: Mechanisms, efficacy, and safety (a review). Pharmaceutical Chemistry Journal. 38. 11. 2004. 590–596. 0091-150X. 10.1007/s11094-005-0036-9. 9442971.
  6. Kozeletskaia KN, Grinbaum EB, Zhamsrangiĭn M, Burmistrova VV, Kiselev OI . [The isolation and study of the properties of current influenza A viruses (H1N1) with a natural resistance to remantadine] . ru . Voprosy Virusologii . 35 . 4 . 289–293 . 1990 . 1701588 .
  7. Kozeletskaia KN, Karginov VA, Kiseleva OI, Mishin VP, Grinbaum EB, Burmistrova VV . [The origin of resistance to chemicals of naturally occurring isolates of influenza A virus] . ru . Vestnik Rossiiskoi Akademii Meditsinskikh Nauk . 9 . 36–41 . 1995 . 7580412 .
  8. Krapivin SV, Sergeeva SA, Morozov IS . [A spectral analysis of the effect of adapromine on brain bioelectrical activity] . ru . Eksperimental'naia i Klinicheskaia Farmakologiia . 55 . 3 . 6–8 . 1992 . 1458170 .
  9. Krapivin SV, Sergeeva SA, Morozov IS . Comparative analysis of the effects of adapromine, midantane, and bromantane on bioelectrical activity of rat brain. Bulletin of Experimental Biology and Medicine. 125. 2. 1998. 151–155. 0007-4888. 10.1007/BF02496845. 21940190.
  10. Krapivin SV, Voronina TA . [Comparative quantitative pharmacological-EEG analysis of the effects of psychostimulants] . ru . Vestnik Rossiiskoi Akademii Meditsinskikh Nauk . 6 . 7–16 . 1995 . 7627000 .
  11. Krapivin SV, Sergeeva SA, Morozov IS, Dulpe IU . Spectral analysis of the effect of midantane on bioelectrical activity of the rat brain. Bulletin of Experimental Biology and Medicine. 112. 1. 1991. 975–978. 0007-4888. 10.1007/BF00841147. 22469427.
  12. Morozov IS, Ivanova IA, Lukicheva TA . Pharmaceutical Chemistry Journal. 35. 5. 2001. 235–238. 0091-150X. 10.1023/A:1011905302667. Actoprotector and Adaptogen Properties of Adamantane Derivatives (A Review). 29475883.
  13. Peeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E . Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine . The European Journal of Neuroscience . 19 . 8 . 2212–2220 . April 2004 . 15090047 . 10.1111/j.0953-816X.2004.03297.x . 19479968 .
  14. US . 3352912 . Prichard WW . Adamantanes and tricyclo[4. 3. 1. 1 3.8] undecanes . patent . 1967-11-14 . 1964-06-18 . EI Du Pont de Nemours and Co.
  15. Aldrich PE, Hermann EC, Meier WE, Paulshock M, Prichard WW, Snyder JA, Watts JC . Antiviral agents. 2. Structure-activity relationships of compounds related to 1-adamantanamine . Journal of Medicinal Chemistry . 14 . 6 . 535–543 . June 1971 . 5091970 . 10.1021/jm00288a019 .

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