Nialamide Research Articles

Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation.

Mitochondrial dysfunction and oxidative stress play a key role in ischemia/reperfusion (I/R) induced brain injury. We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. We demonstrate here that nialamide (NM), a non-selective monoamine oxidase (MAO) inhibitor, upregulated Ublqn1 and protected neurons from oxygen-glucose deprivation- and I/R-caused cell death in in vitro and in vivo, respectively. Post-ischemic administration of the NM in a stroke mouse model even at 3h following I/R still reduced neuronal injury and improved functional recovery and survival. Treating stroke animals with NM also increased the association of Ubqln1 with mitochondria and decreased the total oxidized and polyubiquitinated protein levels. Intriguingly, NM-enhanced proteostasis was also associated with reduced I/R-caused neuroinflammation, as reflected by attenuated activation of microglia and astrocytes as well as reduced TNF-α level. Thus, our results suggest that MAO inhibition-induced neuroprotection following I/R involves improved proteostasis and reduced neuroinflammation.

Detection of oxidative mutagenesis by isoniazid and other hydrazine derivatives in Escherichia coli WP2 tester strain IC203, deficient in OxyR: strong protective effects of rat liver S9

Strain IC203, deficient in the OxyR function, was sensitive to both cytotoxic and mutagenic effects of isoniazid (INH) whereas its parent, WP2 uvrA/pKM101, was resistant to these effects. Four other hydrazine compounds, hydrazine hydrate (HZH), phenylhydrazine (PHZ), hydralazine (HLZ) and nialamide (NLD), were mutagenic in WP2 uvrA/pKM101. Increases in mutagenicity were observed in IC203 for HZH and PHZ but not for HLZ and NLD. Growth inhibition zones by HZH, PHZ and NLD were larger in IC203 than in WP2 uvrA/pKM101. The enhancements in the effects of INH, HZH and PHZ in IC203 with respect to its oxyR + parent are considered to be caused by the production of reactive oxygen species. This is consistent with its inhibition in IC203 by S9 from liver of uninduced rats, probably through the action of catalase. Mutagenicities of INH, PHZ and HLZ were low in strains IC204, a derivative of WP2 uvrA carrying a deletion of the umuDC genes, and IC206, a derivative of IC204 deficient in the MutY glycosylase. In these strains, HZH and NLD induced a high level of revertants which carry suppressor mutations resulting exclusively from G:C–A:T transitions, thus suggesting a direct reaction of the two hydrazines with cytosine.

Differential effects of nialamide and clomipramine on serotonin efflux and autoreceptors

Serotonin (5-HT) activity in vivo and in vitro was evaluated in rats following acute and chronic administration of the antidepressants nialamide (NMD) and clomipramine (CMI). The 5-HT motor syndrome was used as an index of in vivo serotonergic function. In vitro, 3H-5-HT uptake, potassium-evoked 3H-5-HT release and 5-HT autoreceptor activity were evaluated as measures of presynaptic function. Repeated injections of NMD abolished the 5-methoxy-N, N-dimethyltryptamine (5-MeODMT)-induced motor syndrome and the ability of 5-methoxytryptamine (5-MEOT) to attenuate the potassium-evoked release of 3H-5-HT. Autoreceptor subsensitivity was associated with a marked increase in basal and potassium-evoked 3H-5-HT release. In contrast, acute NMD, and acute and chronic CMI did not affect the expression of the motor syndrome or alter 3H-5-HT release or autoreceptor activity. Acute and chronic injections of NMD enhanced 3H-5-HT uptake. The results suggest that the antidepressant efficacy of monoamine oxidase inhibitor (MAOI) antidepressant may be related to their ability to increase endogenous levels of 5-HT and thereby produce a subsensitivity of 5-HT 1 type receptors. This subsensitivity is reflected both by attenuation of the motor syndrome and enhanced 5-HT neurotransmission resulting in part from autoreceptor down-regulation.

Stimulatory effect of N-methyl aspartate on locomotor activity and transmitter release from rat nucleus accumbens

N-Methyl-aspartate (NMA), an agonist at central glutamate receptors, elicitd prolonged and intense locomotor activity when injected into the nucleus accumbens septi (NAS) in subconvulsive doses (3–10 μg bilaterally). This effect was antagonised by intra-accumbens injection of the specific NMA antagonist, aminophosphonovaleric acid (APV) in a dose (3.0 μg bilaterally) that was without intrinsic effect when given on its own. Intra-accumbens injection of APV also suppressed locomotor hyperactivity elicited by intra-acumbens injection of DA (50 μg bilaterally) in rats pretreated with nia lamide. In vitro release of [ 3H]-acetylcholine in accumbens tissue slices was significantly increased in the presence of NMA (30 μM) or N-methyl-D-aspartate (NMDA) (15 μM). Both effects were antagonised by APV (30 μM). Similar results were obtained with tissue slices of rat corpus striatum. These results suggest that locomotor stimulation by intra-accumbens NMA is mediated by an action on the mesolimbic dopaminergic neuron, either directly or via a cholinergic interneuron. In addition, activity at the glutamate synapse may be enhanced by the presence of DA affecting glutamate release and/or reuptake.

The effect of imipramine and nialamide on the accumulation of serotonin in snail (Helix pomatia) nervous tissue.

Sowohl Nervengewebe als auch definierte Nervenzellsomata (GSC) vonHelix pomatia konnen zwar14C-Serotonin aufnehmen, aber nur im Nervengewebe wird es zu14C-Hydroxyindolessigsaure umgewandelt. Die Wirkung von Imipramin und Nialamid macht wahrscheinlich, dass Serotonin auf zwei Wegen inaktiviert wird, d. h. durch enzymatische Oxydation und durch Wiederaufnahme in die synaptischen Boutons.

CPT and VCRT performances as functions of imipramine and nialamide.

CPT and VCRT performances as functions of imipramine and nialamide.

NIALAMIDE (NIAMID) IN ANGINA PECTORIS: Report of a Double-blind Trial

NIALAMIDE (NIAMID) IN ANGINA PECTORIS: Report of a Double-blind Trial

"Niamid" in Mongolism

"Niamid" in Mongolism