Central Stimulants. Chemistry and Structure-Activity Relationship of Aralkyl Hydrazines

Abstract

The replacement of an amino or alkylamino group by a hydrazino or alkyl hydrazino moiety in a variety of aralkylamines has yielded a group of potent central stimulants which produce their effect by a dual mechanism: (1) direct stimulation of the central nervous system (analeptic action), and (2) powerful inhibition of the enzyme monoamine oxidase (MAO) which is responsible for the metabolic destruction of endogenous central excitatory hormones. Definite structure-activity relationships have been established and will be discussed. One of the compounds, N-aminoamphetamine, displayed forty times the MAO inhibitory potency of iproniazid (Marsilid). The synthesis of the aralkyl hydrazines was accomplished via the reductive hydrazinolysis of phenyl-alkanones or reaction of hydrazine with a phenylalkyl halide. The nature of the products obtained was dependent on the reaction conditions. It is demonstrated also that the Raney nickel cleavage of substituted hydrazines constitutes a convenient means of obtaining pure primary and secondary amines.

Monoamine Oxidase Inhibitors

“…This does not agree with the finding of Biel et al (88), who reported that XX was active only in uiuo and inactive at Substitution of either or both nitrogens of XX by a carbethoxy group resulted in decreased inhibitory activity.…”

Alcalóides indólicos isolados de espécies do gênero Aspidosperma (Apocynaceae)

“…Segundo a literatura, alcalóides indólicos constituem bons marcadores quimiotaxonômicos para classificação botânica das espécies de Aspidosperma 10,[25][26][27] . Biologicamente, muitos alcalóides indólicos agem provavelmente nos sistemas neurotransmissores opiáceos, GABAérgicos, colinérgicos, muscarínicos, serotoninérgicos e dopaminérgicos 28,29 . Por isso, são empregados largamente como hipotensor arterial, simpatolítico, diurético, vasoconstrictor periférico, estimulante respiratório, anestésico, agente bloqueador adrenérgico, espasmogênico intestinal, sedativo e relaxante do músculo esquelético 20,30,31 .…”

The inhibition of monoamine oxidase by arylalkylhydrazines

“…The arylalkylhydrazines were obtained by boiling the corresponding arylalkyl chloride or bromide with 5 molar equivalents of hydrazine hydrate in ethanol. The free bases were then converted into their crystalline hydrochlorides by addition of HCI in ether to a solution of the base in ethanol and ether (Biel et al 1959).…”