Memantine, amantadine, and L-deprenyl potentiate the action of L-DOPA in monoamine-depleted rats

Abstract

Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and alpha-methyl-p-tyrosine. In the present study memantine (2.5, 5.0 mg/kg), amantadine (10, 20 mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0 mg/kg) and L-dopa (50, 100 mg/kg, +benserazide, 100 mg/kg). At higher doses, memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10 mg/kg) and L-dopa (100, 200 mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-dopa produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-dopa with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl.

Functionalized Nanodiamonds Part I. An Experimental Assessment of Diamantane and Computational Predictions for Higher Diamondoids

“…The combined extracts were washed with an aqueous NaHSO 3 solution and water, and dried over Na 2 SO 4 ; excess solvents were removed in vacuo. The residue was analyzed by GC-MS and showed conversion of approximately 75 %; 1-iododiamantane (17), 4-iododiamantane (18), and 3-iododiamantane (19) (9). The reaction mixture was separated by column chromatography (pentane as eluent), which gave a pure sample of 1-iododiamantane 17 (195 mg, 39 %) and a mixture of 18 and 19 (137 mg, 27 %).…”

“…(8)], followed by proton loss (in solution) from the alkane radical cation forming an alkyl radical [Eq. (9)] that couples with the aromatic reagent [Eq. (10)].…”

“…0.2-0.5 nm) and macromolecular small diamonds (ca. 1-100 nm), often referred to as "nanodiamonds", [7] make them particularly attractive for the preparation of pharmacologically active compounds (pronounced membrane activity [8] due to the high lipophilicity of the aliphatic core structure is expected, as for adamantane [9] ), polymers with high rigidity, [10] and hybrid materials. [11] As higher diamondoids are now accessible in sizeable quantities from crude oil, [12][13][14] the quest for their selective functionalization arises.…”

Effects of N-propargyl-1-(R)aminoindan (rasagiline) in models of motor and cognition disorders

“…Motor activity was scored for the duration of 10 hours in activity cages, as given under haloperidol. In a variant of this test (Skuza et al, 1994), rats were treated with reserpine (5 mg/kg s.c.) then a-MpT (250mg/kg i.p.) 24 and 3 hours before scoring for motor activity.…”

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine

“…In patients with Parkinson's disease, amantadine treatment is an independent predictor of improved survival (Uitti et al, 1996), and is especially effective at controlling motor fluctuations induced by L-DOPA (Verhagen Metman et al, 1998). In rat models of parkinsonism, amantadine reverses neuroleptic-induced catalepsy , and potentiates the stimulant action of L-DOPA following cerebral catecholamine depletion (Skuza et al, 1994).…”