Disease relevance of NSC77935

• The implication of this finding is that the possible application of 4-phenylpyridine in the MPTP-induced Parkinson's disease is limited by its potentiation on the neuromuscular blocking action of MPTP [1].

High impact information on NSC77935

• Pargyline and 4-phenylpyridine, the monoamine oxidase type B inhibitors, mimicked the depressant effect of L-deprenyl on the EPSP [2].
• Pretreatment with 50 microM 4-phenylpyridine, reduced IC50 (concentration for 50% inhibition of twitch amplitude) values of MPTP from 53 to 18 microM and d-tubocurarine from 0.7 to 0.3 microM, respectively [1].
• Potentiation by 4-phenylpyridine (a MAO-B inhibitor) on the neuromuscular blocking action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in mouse phrenic nerve-diaphragm [1].
• Amine N-methyltransferases in the brains of humans, monkeys, mice, rabbits and rats, as well as two homogeneous enzymes isolated from rabbit liver, are capable of N-methylating 4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenyltetrahydropyridine (MPTP), and 4-phenylpyridine to 1-methyl-4-phenylpyridinium ion (MPP+) [3].
• C57 black mice were injected repeatedly with maximal tolerated doses of 2 chemical analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); 4-phenylpyridine and 4-phenyl-1,2,3,6-tetrahydropyridine [4].

Biological context of NSC77935

• In isolated inner membranes the inhibition of NADH oxidation via the respiratory chain by 4-phenylpyridine is much greater than by MPP+ [5].

Anatomical context of NSC77935

• This is in accord with the fact that MPP+ is rapidly concentrated in the mitochondria by an energy-dependent process, while 4-phenylpyridine seems to enter passively with the concentration gradient [5].

Associations of NSC77935 with other chemical compounds

• Of the compounds tested, 4-phenyl-1,2,3,6-tetrahydropyridine (PTP), 4-phenylpyridine and 4-phenylpiperidine strongly and dose-dependently inhibited MAO-A and -B activity [6].
• 4-Phenyl-N-methylpyridinium (MPP+), the oxidation product of the neurotoxic amine MPTP, is considerably more inhibitory to the oxidation of NAD+-linked substrates in intact mitochondria in State 3 than is 4-phenylpyridine [5].
• From on-chip dilution-based mass spectrometric titrations of Zn-porphyrin 1 with pyridine (2) or 4-phenylpyridine (4) in acetonitrile Ka-values of 4.6 +/- 0.4 x 10(3) M(-1) and 6.5 +/- 1.2 x 10(3) M(-1), respectively, were calculated [7].

Gene context of NSC77935

• Inhibition of PTP and 4-phenylpiperidine was MAO-A-selective, while that by 4-phenylpyridine was MAO-B-selective [6].
• The enzyme nicotinamide N-methyltransferase (NNMT) can covert otherwise harmless pyridines such as 4-phenylpyridine into MPP+ like compounds [8].

Analytical, diagnostic and therapeutic context of NSC77935

• Potentiation of MPTP by 4-phenylpyridine on the neuromuscular blockade in mouse phrenic nerve-diaphragm [1].

References