6-HYDROXYDOPAMINE HYDROCHLORIDE

Description

6-Hydroxydopamine hydrochloride (6-OHDA) is a neurotoxin, commonly used to induce Parkinson′s disease (PD). 6-OHDA causes death of dopaminergic neurons in substantia nigra pars compacta progressively mimicking PD. 6-OHDA is highly oxidizable and cannot cross blood brain barrier. 6-OHDA exerts cytotoxicity by generating reactive oxygen species, initiating cellular stress and cell death. 6-OHDA leads to neuronal cell death in many in vitro models like primary neuronal culture, human neuroblastoma cell line and rat adrenal pheochromocytoma cell line, PC12.

Uses

6-hydroxydopamine hydrochloride has been used:

• to induce Parkinson′s disease (PD) in rats
• to analyse cytotoxic effect of 6-OHDA on PC12 cell line
• to induce noradrenergic (NA) neuron deletion from the locus-coeruleus

General Description

Beige solid.

Air & Water Reactions

Hygroscopic. Water soluble.

Reactivity Profile

A weak acid. Materials in this group are generally soluble in water. The resulting solutions contain moderate concentrations of hydrogen ions and have pH's of less than 7.0. They react as acids to neutralize bases. These neutralizations generate heat, but less or far less than is generated by neutralization of inorganic acids, inorganic oxoacids, and carboxylic acid. They usually do not react as either oxidizing agents or reducing agents but such behavior is not impossible. Many of these compounds catalyze organic reactions.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition 6-HYDROXYDOPAMINE HYDROCHLORIDE emits very toxic fumes.

Fire Hazard

Flash point data for 6-HYDROXYDOPAMINE HYDROCHLORIDE are not available. 6-HYDROXYDOPAMINE HYDROCHLORIDE is probably combustible.

Biological Activity

Selective catecholaminergic neurotoxin. Depletes brain catecholamine levels via uptake and accumulation by a transport mechanism specific to these neurons. Causes almost complete destruction of nigral dopaminergic neurons and their striatal terminals when injected into the substantia nigra of rats, producing an animal model of Parkinson's disease.

Mechanism of action

The biochemical mechanism of toxicity of 6-Hydroxydopamine hydrochloride (6-OHDA) is as follows: 6-OHDA has two modes of action: it readily forms free radicals and it is a potent inhibitor of the mitochondrial respiratory chain complexes I and IV. The inhibition of respiratory enzymes by 6-OHDA is reversible and insensitive to free radical scavengers and iron chelators, except for desferrioxamine. Moreover, free radicals are not involved in the interaction between 6-OHDA and the respiratory chain, and the two mechanisms are biochemically independent, although they may act synergistically in vivo.