The effect of the monoamine oxidase inhibitor isocarboxazid on the canine metabolism of the cell-differentiating agent hexamethylene bisacetamide

  title={The effect of the monoamine oxidase inhibitor isocarboxazid on the canine metabolism of the cell-differentiating agent hexamethylene bisacetamide},
  author={Barbara A. Conley and Gerald F. Sewack and Merrill J. Egorin and Babu Subramanyam and John G. Page and Charles K. Grieshaber},
  journal={Cancer Chemotherapy and Pharmacology},
SummaryThe acute toxicities of the cellular differentiating agent hexamethylene bisacetamide (HMBA) in humans and animals include CNS toxicity (agitation, somnolence, seizures, hallucinations) and an anion-gap metabolic acidosis,N-Acetyl-1,6-diaminohexane (NADAH), the first metabolite of HMBA, is as active as the parent compound in causing differentiation of leukemic cells in vitro, whereas 6-acetamidohexanoic acid (6AcHA), which is formed by the oxidation of NADAH in the presence of monoamine… 

Amide exchange reaction: a simple and efficient CuO catalyst for diacetamide synthesis

A highly copper-catalysed amide exchange reaction of hexamethylenediamine (HDA) with CH3CN and H2O for the synthesis of hexamethylenebisacetamide (HMBA) without an organic solvent or gas protection

m6A RNA Methylation Regulators Impact Prognosis and Tumor Microenvironment in Renal Papillary Cell Carcinoma

A two-gene prognostic risk model including IGF2BP3 and HNRNPC was constructed and could predict overall survival of PRCC patients from the Cancer Genome Atlas dataset and predicted the three most significant small molecule drugs that potentially inhibit PRCC.

Approaches to optimal dosing of hexamethylene bisacetamide

Whether exposure to HMBA could be individualized and maximized without resulting in intolerable toxicity to patients was investigated and which factors would predispose a patient to the development of acute toxicity during treatment with HMBA were determined.



Effects of the monoamine oxidase inhibitor, tranylcypromine, on induction of HL60 cell differentiation by hexamethylene bisacetamide and N-acetyl-1,6-diaminohexane.

The hypothesis that MAO catalyzed metabolism of NADH to AcHA is an inactivation pathway is supported and may provide the basis for a clinical trail in which HMBA metabolism is modulated with concurrent tranylcypromine therapy.

Identification of metabolites of the cell-differentiating agent hexamethylene bisacetamide in humans.

Hexamethylene bisacetamide, a compound which in vitro induces differentiation in a wide variety of human and animal cancer cell lines, is being investigated in phase I clinical trials and metabolites identified included the major metabolite, 6-acetamidohexanoic acid.

Phase I and pharmacologic study of hexamethylene bisacetamide in patients with advanced cancer.

Based on this trial, the maximum tolerated and recommended phase II doses for HMBA administered on this schedule are 33.6 and 24 g/m2/d, respectively, since steady-state HMBA levels at these doses were only approaching the lower limit demonstrated for in vitro differentiating effectiveness.

Induction of differentiation of human promyelocytic leukemia cells (HL60) by metabolites of hexamethylene bisacetamide.

6-acetamidohexanoic acid, when combined with HMBA or NADAH at various concentrations and ratios, enhanced the differentiation of HL60 cells induced by these two compounds, which may provide some insight into the mechanism of HMBA-induced cellular differentiation.

A new group of potent inducers of differentiation in murine erythroleukemia cells.

A group of compounds, polymethylene bisacetamides (acetylated diamines), which are potent inducers of erythroid differentiation in murine eryTHroleukemia cells are identified and introduced through varying numbers of methylenes substantially increased the effectiveness of these compounds.

Inducers of erythroleukemic differentiation. Relationship of structure to activity among planar-polar compounds.

Effective "dimerization" of dimethyl sulfoxide through a linear polymethylene chain increases its inducing activity by a magnitude similar to that observed when N-methylacetamide is effectively dimerized in such a manner.

Prolonged infusion of hexamethylene bisacetamide: a phase I and pharmacological study.

It was apparent that the duration of HMBA exposure was an additional significant variable in predicting the magnitude of thrombocytopenia, and the maximum tolerated and recommended phase II doses for HMBA administered on this schedule were 20 and 15.8 g/m2/d, respectively.

Phase I clinical and pharmacokinetic study of hexamethylene bisacetamide (NSC 95580) administered as a five-day continuous infusion.

Hexamethylene bisacetamide (HMBA), a potent differentiating agent, was tested in patients with refractory, solid tumors and metabolic acidosis and neurotoxicity, consisting of agitation, hallucinations, confusion, and alteration of consciousness, were dose dependent and dose limiting.