Pomponi M

References (9)

Title : Inhibition of acetylcholinesterase by physostigmine analogs: conformational mobility of cysteine loop due to the steric effect of the alkyl chain - Gavuzzo_2002_J.Biochem.Mol.Toxicol_16_64
Author(s) : Gavuzzo E , Pomponi M
Ref : J Biochem Mol Toxicol , 16 :64 , 2002
Abstract : The effect of a series of physostigmine analogs on acetylcholinesterase activity was investigated. The second-order rate constant k(on) of the enzyme-inhibitor complex correlates with the conformational positioning of aromatic residues, especially Trp84, in the transition state complex. The van der Waals interactions are an important structural element of this conformational change. A transient mobility of the cysteine loop (Cys67-Cys94) was confined only to the presence of a significant steric effect. Even with this limitation, however, the steric effect seems to be an appropriate model for future tests on the "back door" hypothesis involving facilitated opening for faster product clearance.
ESTHER : Gavuzzo_2002_J.Biochem.Mol.Toxicol_16_64
PubMedSearch : Gavuzzo_2002_J.Biochem.Mol.Toxicol_16_64
PubMedID: 11979423

Title : Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4- tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice - Capone_1999_Neurobiol.Learn.Mem_71_301
Author(s) : Capone F , Oliverio A , Pomponi M , Marta M , Gatta F , Pavone F
Ref : Neurobiol Learn Mem , 71 :301 , 1999
Abstract : The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) characterized by an alkyl chain in the molecular structure which ameliorates the penetrability of the compound into the central nervous system. THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and that are much lower than the doses reported to be effective for THA in animal models. From the data reported it seems that the new compound could be interesting for therapeutic purposes.
ESTHER : Capone_1999_Neurobiol.Learn.Mem_71_301
PubMedSearch : Capone_1999_Neurobiol.Learn.Mem_71_301
PubMedID: 10196108

Title : Effects of cholinergic drugs on neocortical EEG and flash-visual evoked potentials in the mouse - Tebano_1999_Neuropsychobiology_40_47
Author(s) : Tebano MT , Luzi M , Palazzesi S , Pomponi M , Loizzo A
Ref : Neuropsychobiology , 40 :47 , 1999
Abstract : The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.05, 0. 1, 0.2 mg/kg) and heptylphysostigmine (HEP; 0.5, 2, 6 mg/kg) on electroencephalographic (EEG) activity and flash visual evoked potentials (f-VEP) in the occipital cortex were compared in DBA/2 mice. EEG spectral analysis of awake periods showed that PHY at all doses and HEP at 2 mg/kg induced an increase of power in the 4.25- to 7-Hz frequency band. Furthermore, PHY at the higher doses and HEP at all doses induced a decrease of power in the 7.25- to 12-Hz frequency band, while the lower doses of PHY (0.01, 0.025 mg/kg) produced an increase of this band. EEG effects elicited by the two drugs were similar, when doses displaying analogous biochemical effects (acetylcholinesterase inhibition) were used (i.e. 0.01 and 0. 025 mg/kg of PHY versus 0.5 and 2 mg/kg of HEP). PHY and HEP induced similar changes in f-VEPs. Amplitudes of early and late components (P1N1, N1P2, P4N4 and particularly N1P3) were enhanced, while amplitudes of middle components were depressed after all doses. The peak latency measures were generally delayed, even though, after the lower doses, a trend to a latency reduction was evident in late components. This finding might indicate a possible effect on stimulus speed diffusion by 'low therapeutic' doses, analogous to the ones used in men. Our data show that both drugs are effective in modifying EEG and f-VEP parameters connected with brain cholinergic function, although in a very narrow dose range.
ESTHER : Tebano_1999_Neuropsychobiology_40_47
PubMedSearch : Tebano_1999_Neuropsychobiology_40_47
PubMedID: 10420101

Title : The role of TRP84 in catalytic power and the specificity of AChE - Pomponi_1998_Biophys.Chem_72_239
Author(s) : Pomponi M , Sacchi S , Colella A , Patamia M , Marta M
Ref : Biophysical Chemistry , 72 :239 , 1998
Abstract : The structure-function relationship between the alkaloids physostigmine, physovenine and the three structurally related compounds were investigated by employing kinetic studies and molecular modeling. Crystallographic data from the X-ray conformation of the Torpedo californica acetylcholinesterase complex together with the transition state analog inhibitor m-(N,N,N,-Trimethylammonio) trifluoroacetophenone (TMTFA) was used as template onto which inhibitors were superimposed. Among the structural elements of the active site, TRP84 residue shows a versatile role. In fact, its aromatic electrons not only can be employed in pi-cation interactions, as is the case for ACh, but they can also provide a polarizable surface for van der Waals and London interactions.
ESTHER : Pomponi_1998_Biophys.Chem_72_239
PubMedSearch : Pomponi_1998_Biophys.Chem_72_239
PubMedID: 9691268

Title : Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE - Pomponi_1997_FEBS.Lett_409_155
Author(s) : Pomponi M , Marta M , Colella A , Sacchi S , Patamia M , Gatta F , Capone F , Oliverio A , Pavone F
Ref : FEBS Letters , 409 :155 , 1997
Abstract : A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.
ESTHER : Pomponi_1997_FEBS.Lett_409_155
PubMedSearch : Pomponi_1997_FEBS.Lett_409_155
PubMedID: 9202137

Title : The effect of heptyl-physostigmine, a new cholinesterase inhibitor, on the central cholinergic system of the rat - De Sarno_1989_Neurochem.Res_14_971
Author(s) : De Sarno P , Pomponi M , Giacobini E , Tang XC , Williams E
Ref : Neurochemical Research , 14 :971 , 1989
Abstract : Heptyl-physostigmine (Heptyl-Phy; MF-201) is a new carbamate derivative of physostigmine (Phy) with greater lipophilicity and longer inhibitory action on cholinesterase (ChE) activity than the parent compound. Following single dose administration of 5 mg/kg heptyl-Phy i.m., maximal whole brain acetylcholinesterase (AChE) inhibition (82%) if reached at 60 min. Inhibition of plasma BCHE butyrylcholinesterase (BCHE) remains close to the steady state level (60%) between 120 and 360 min. At 360 min, whole brain AChE activity is still 67% inhibited compared to controls. Inhibition of AChE activity displays brain regional differences which are more significant at 360 min. At this time point, AChe activity in cerebellum is only 40% inhibited while frontal cortex and medial septum are still 80% inhibited. Increases in acetylcholine (ACh) levels also show regional differences, however, there is no direct relationship between AChE inhibition and ACh increase. The electrically evoked [3H]ACh release in cortical slices was inhibited only by the highest concentration of heptyl-Phy tested (10(-4) M). At this concentration ChE activity was 97% inhibited in vitro. In conclusion, our results demonstrate that heptyl-Phy compares favorably to other reversible cholinesterase inhibitors (ChEI), particularly to Phy as far as producing a more long-lasting inhibition of AChE and a more prolonged increase of ACh in brain with less severe side effects. Therefore, it represents an interesting candidate for cholinomimetic therapy of Alzheimer disease (AD).
ESTHER : De Sarno_1989_Neurochem.Res_14_971
PubMedSearch : De Sarno_1989_Neurochem.Res_14_971
PubMedID: 2608162

Title : New analogs of physostigmine: alternative drugs for Alzheimer's disease? - Marta_1988_Life.Sci_43_1921
Author(s) : Marta M , Castellano C , Oliverio A , Pavone F , Pagella PG , Brufani M , Pomponi M
Ref : Life Sciences , 43 :1921 , 1988
Abstract : The synthesis of a series of physostigmine analogs, in which the methylcarbamyl group has been substituted with monoalkylcarbamyl, dimethyl- and diethylcarbamyl groups, is reported. These compounds were prepared with the aim of investigating their possible therapeutic effects in the treatment of Alzheimer's type dementia. The new analogs of physostigmine are inhibitors of acetylcholinesterase from Electroforus electricus, with a value of the reactivation constant, k3 smaller than the one of physostigmine. The percentage of anticholinesterase activity in vitro and in vivo, the acute toxicity and some behavioural effects were also evaluated for selected derivatives. The reactivation constant, in vitro, supports the view that the derivatives described would be more suitable for therapeutic use than physostigmine.
ESTHER : Marta_1988_Life.Sci_43_1921
PubMedSearch : Marta_1988_Life.Sci_43_1921
PubMedID: 3200115

Title : A long-lasting cholinesterase inhibitor affecting neural and behavioral processes - Brufani_1987_Pharmacol.Biochem.Behav_26_625
Author(s) : Brufani M , Castellano C , Marta M , Oliverio A , Pagella PG , Pavone F , Pomponi M , Rugarli PL
Ref : Pharmacol Biochem Behav , 26 :625 , 1987
Abstract : A series of analogues of physostigmine were prepared with the aim of investigating their inhibitory effects on acetylcholinesterase in the treatment of Alzheimer's disease. One of the isomers prepared was evaluated for its anticholinesterase activity in vivo, acute toxicity, and some behavioral effects. This compound was a competitive inhibitor of the enzyme and was found to antagonize the stimulating effect produced by scopolamine on locomotor activity and to facilitate memory consolidation.
ESTHER : Brufani_1987_Pharmacol.Biochem.Behav_26_625
PubMedSearch : Brufani_1987_Pharmacol.Biochem.Behav_26_625
PubMedID: 3575379

Title : Anticholinesterase activity of a new carbamate, heptylphysostigmine, in view of its use in patients with Alzheimer-type dementia - Brufani_1986_Eur.J.Biochem_157_115
Author(s) : Brufani M , Marta M , Pomponi M
Ref : European Journal of Biochemistry , 157 :115 , 1986
Abstract : The anticholinesterase activity of a new carbamate, heptylphysostigmine, was studied in vitro. This compound is a competitive inhibitor of acetylcholinesterase (or true cholinesterase) having Ki = (1 +/- 0.5) X 10(-7) M. The inhibition was instantaneous at the onset and did not diminish with prolonged incubation of the drug and enzyme.
ESTHER : Brufani_1986_Eur.J.Biochem_157_115
PubMedSearch : Brufani_1986_Eur.J.Biochem_157_115
PubMedID: 3709528