Anti-inflammatory and Analgesic Activity of Azaadamantanes - Analogues of Amantadine

The anti-inflammatory and analgesic activity of three azaadamantane analogues of amantadine 1 was investigated. The tested azaadamantanes containing nitrogen atoms in the polycyclic framework were: 5,7-dimethyl-1,3-diazaadamantane-6-one 2, 6-amino-5,7-dimethyl-1,3-diazaadamantane 3 and 7-amino-1,3,5-triazaadamantane 4. Experiments were carried out on male mice of CD1 and CBA lines. Compounds were administered intraperitoneally at doses of 20 and 50 mg/kg. Anti-inflammatory activity was studied on the standard models of inflammatory edema induced by histamine or concanavaline inflammation by injecting the phlogogens in the aponeurosis of the hind paw of mice. The analgesic activity was assessed using the hot plate and acetic writhing tests. It is shown that the introduction of heteroatoms into the adamantane core does not reduce the anti-inflammatory activity of diazaadamantanes (2, 3) and enhances that of triazaadamantane (4) compared to amantadine. Modification of the adamantane backbone with nitrogen atoms leads to a change in the analgesic properties of the molecule, which is manifested as hyperalgesia in the acetic writhing test. This phenomenon is presumably related to the effect of azaadamantanes on nocigenic transient receptor potential channels (TRPV1).