Abstract: Many hydrazides such as iproniazid, isocarboxazide, and nialamide are monoamine oxidase (MAO) inhibitors, and are used clinically for the treatment of mental depres- sion, angina pectoris and hypertension. High toxicity and some unpleasant side effects are their main drawbacks. The aim of the present work was to prepare various hydra- zides in an attempt to search for effective yet less toxic compounds. Oxalyl dihydrazides were reported to be very active as MAO inhibitors. It is well known that ethers and thioethers have high penetrating power. A series of dihydrazides carrying ether or thio- ether moiety was therefore synthesized. Phenylpiperazino hydrazides as well as dihydra- zides containing amino linkage were also prepared since nitrogen is an isostere of oxygen or sulphur. Aza-, oxa-, and thia-dibasic acid dihydrazides, which were prepared on interaction of the corresponding diesters with hydrazine hydrate, were condensed with aldehydes or ketones carrying various alkyl substituents. The hydrazones (XI, XII, XIII) so formed were reduced with potassium boron hydride, affording the corresponding N²-substituted hydrazides (Ⅴ,Ⅵ,Ⅶ,Ⅷ). Benzyl and 2-phenethyl hydrazides were prepared on treatment of the corresponding diesters with benzyl hydrazine or 2-phenethyl hydrazine. (4-Phenyl-l-piperazino)-acetyl hydrazide (IX_a) was formed on condensation of the cor- responding ethyl ester with 86% hydrazine, but N,N'-bis-(4-phenyl-l-piperazinoacetyl)- hydrazide (X) was obtained when 50% hydrazine hydrate was employed. Pharmacological tests revealed that most compounds prepared were active as MAO inhibitors. 4-Thiaheptan-l,7-di-oyl bis-isopropyl-hydrazide (VII_c) had the most favourable therapeutic index, and was sent for clinical trials.