Disease relevance of CCRIS 7301

• Lazabemide therapy did not induce clinically significant arrhythmias [1].
• Fifty-one patients with PD who did not have clinically apparent heart disease were randomized in a double-blind fashion to receive either lazabemide (n = 25) or placebo (n = 26) treatments [1].
• Therefore, it is natural to expect that monoamine oxidase inhibitors, deprenyl or lazabemide, could exhibit beneficial effects on parkinsonism, i.e. symptomatic effects [2].

Psychiatry related information on CCRIS 7301

• AIMS : To assess whether lazabemide, a reversible selective MAOB inhibitor, promotes smoking cessation [3].
• Lazabemide for the treatment of Alzheimer's disease: rationale and therapeutic perspectives [4].

High impact information on CCRIS 7301

• Most of them were MAO B inhibitors and those bearing a substituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 microM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37,000 for 16a [5].
• Antioxidant activity of the monoamine oxidase B inhibitor lazabemide [6].
• Under physiologic-like conditions, lazabemide inhibited lipid peroxidation in a highly concentration-dependent manner [6].
• In this study, the intrinsic antioxidant activity of lazabemide, a potent and reversible inhibitor of monoamine oxidase B (MAO-B), was tested in a membrane-based model of oxidative stress [6].
• The IC50 values for lazabemide and Ro 16-6491, respectively, were: 86 microM and 90 microM for NA uptake; 123 microM and 90 microM for 5HT uptake; > 500 microM and > 1000 microM for DA uptake [7].

Biological context of CCRIS 7301

• Pharmacokinetics and pharmacodynamics of single and multiple doses of the MAO-B inhibitor lazabemide in healthy subjects [8].
• CONCLUSIONS: The clinical pharmacology characteristics of lazabemide did not differ markedly after single and multiple oral doses [8].
• Investigation on the structure of the active site of monoamine oxidase-B by affinity labeling with the selective inhibitor lazabemide and by site-directed mutagenesis [9].
• Deamination of 14C-beta-PEA was found to be reduced by lazabemide in a concentration-dependent manner with a Ki value of 17 nM [10].
• The mean decrease of systolic blood pressure was 10 mmHg greater in the lazabemide group than in the placebo group [1].

Anatomical context of CCRIS 7301

• With regard to the effects examined, lazabemide markedly differs from L-deprenyl since it does not interfere with DA uptake nor induce amine release from synaptosomes [7].
• To investigate whether the reversible monoamine oxidase-B (MAO-B) inhibitors lazabemide and Ro 16-6491 have any additional effect on monoamine uptake and release, in vitro experiments were performed on rat forebrain synaptosomes and blood platelets [7].
• The density of MAO-B sites was quantified by the specific binding of the selective inhibitor [3H]Ro 19-6327 (lazabemide) (8 nM) to cortical membranes [11].

Associations of CCRIS 7301 with other chemical compounds

• In vitro effects on monoamine uptake and release by the reversible monoamine oxidase-B inhibitors lazabemide and N-(2-aminoethyl)-p-chlorobenzamide: a comparison with L-deprenyl [7].
• In contrast, the reversible MAO-A inhibitor moclobemide (2.5-10 mg kg(-1)) and the reversible MAO-B inhibitor lazabemide (2.5-10 mg kg(-1)) failed to instigate significant rotational behaviour compared to vehicle [12].
• In the rat renal cortex lazabemide and selegiline both inhibited beta-PEA deamination [13].
• We thought worthwide to evaluate the effect of Ro 41-1049 and lazabemide, both members of a class of highly selective, mechanism-based and reversible inhibitors for MAO-A and MAO B, respectively on the metabolization of beta-PEA by the rat heart [13].
• A sensitive and specific analytical method was developed for determination of Ro 19-6327 (Lazabemide) in human plasma and urine samples to provide pharmacokinetic data from clinical trials [14].

Gene context of CCRIS 7301

• We therefore investigated the activity of the degradative enzyme monoamine oxidase (MAO) and its binding parameters using [3H]Ro 41-1049 (defining MAO-A) and [3H]Ro 19-6327 (Lazabemide; defining MAO-B) in autopsied brain tissue from male cirrhotic patients with HE [15].
• Unexpectedly, the selective MAO-A inhibitor Ro 41-1049 was by far the most potent inhibitor of beta-PEA (20 microM) deamination in the rat heart, while clorgyline, another MAO A inhibitor, and lazabemide, a MAO B inhibitor, had intermediate efficacy; selegiline was found unable to inhibit deamination of beta-PEA [13].
• The specific activity and kinetic behaviour of semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) towards benzylamine, in the rat heart, is affected by in vivo treatment with the non-selective monoamine oxidase (MAO) inhibitor tranylcypromine, but not by the selective MAO-A and -B inhibitors, clorgyline and lazabemide [16].

Analytical, diagnostic and therapeutic context of CCRIS 7301

• To evaluate whether lazabemide has proarrhythmic or hypotensive potency in Parkinson's disease (PD), we conducted an 8-week, double-blind, placcbo-controlled, parallel group study with use of 24-hour ambulatory electrocardiographic (ECG) monitoring [1].

References