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 alkylanalogue 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.[1][2][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.[13]
Synthesis
The first synthesis of adapromine was disclosed in patents by DuPont published in 1967.[14]
^ abLavrova LN, Indulen MK, Ryazantseva GM, Korytnyi VS, Yashunskii VG (1990). "Synthesis and biological activity of some 1-hydroxy-3-aminoalkyladamantanes and their derivatives". Pharmaceutical Chemistry Journal. 24 (1): 35–39. doi:10.1007/BF00769383. ISSN0091-150X. S2CID8544357.
^Gavrilova NA, Frolenko TA, Semichenko ES, Suboch GA (2010). "Synthesis of naphtho[1,2-d]imidazoles containing an adamantyl fragment". Russian Journal of Organic Chemistry. 46 (5): 777–778. doi:10.1134/S1070428010050349. ISSN1070-4280. S2CID94469430.
^Rodionov VN, Sklyarova AS, Shamota TV, Schreiner PR, Fokin AA (2011). "Selective reductive dimerization of homocubane series oximes". Russian Journal of Organic Chemistry. 47 (11): 1695–1702. doi:10.1134/S1070428011110078. ISSN1070-4280. S2CID94472143.
^Leneva IA, Glushkov RG, Gus'kova TA (2004). "Drugs for chemotherapy and prophylaxis of influenza: Mechanisms, efficacy, and safety (a review)". Pharmaceutical Chemistry Journal. 38 (11): 590–596. doi:10.1007/s11094-005-0036-9. ISSN0091-150X. S2CID9442971.
^Kozeletskaia KN, Grinbaum EB, Zhamsrangiĭn M, Burmistrova VV, Kiselev OI (1990). "[The isolation and study of the properties of current influenza A viruses (H1N1) with a natural resistance to remantadine]". Voprosy Virusologii (in Russian). 35 (4): 289–293. PMID1701588.
^Kozeletskaia KN, Karginov VA, Kiseleva OI, Mishin VP, Grinbaum EB, Burmistrova VV (1995). "[The origin of resistance to chemicals of naturally occurring isolates of influenza A virus]". Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (in Russian) (9): 36–41. PMID7580412.
^Krapivin SV, Sergeeva SA, Morozov IS (1992). "[A spectral analysis of the effect of adapromine on brain bioelectrical activity]". Eksperimental'naia i Klinicheskaia Farmakologiia (in Russian). 55 (3): 6–8. PMID1458170.
^Krapivin SV, Sergeeva SA, Morozov IS (1998). "Comparative analysis of the effects of adapromine, midantane, and bromantane on bioelectrical activity of rat brain". Bulletin of Experimental Biology and Medicine. 125 (2): 151–155. doi:10.1007/BF02496845. ISSN0007-4888. S2CID21940190.
^Krapivin SV, Voronina TA (1995). "[Comparative quantitative pharmacological-EEG analysis of the effects of psychostimulants]". Vestnik Rossiiskoi Akademii Meditsinskikh Nauk (in Russian) (6): 7–16. PMID7627000.
^Krapivin SV, Sergeeva SA, Morozov IS, Dulpe IU (1991). "Spectral analysis of the effect of midantane on bioelectrical activity of the rat brain". Bulletin of Experimental Biology and Medicine. 112 (1): 975–978. doi:10.1007/BF00841147. ISSN0007-4888. S2CID22469427.
^Morozov IS, Ivanova IA, Lukicheva TA (2001). "Actoprotector and Adaptogen Properties of Adamantane Derivatives (A Review)". Pharmaceutical Chemistry Journal. 35 (5): 235–238. doi:10.1023/A:1011905302667. ISSN0091-150X. S2CID29475883.
^ abPeeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E (April 2004). "Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine". The European Journal of Neuroscience. 19 (8): 2212–2220. doi:10.1111/j.0953-816X.2004.03297.x. PMID15090047. S2CID19479968.
^ abUS patent 3352912, Prichard WW, "Adamantanes and tricyclo[4. 3. 1. 1 3.8] undecanes", issued 1967-11-14, assigned to EI Du Pont de Nemours and Co
^Aldrich PE, Hermann EC, Meier WE, Paulshock M, Prichard WW, Snyder JA, et al. (June 1971). "Antiviral agents. 2. Structure-activity relationships of compounds related to 1-adamantanamine". Journal of Medicinal Chemistry. 14 (6): 535–543. doi:10.1021/jm00288a019. PMID5091970.
