Scavenging Effects of Dopamine Agonists on Nitric Oxide Radicals

Abstract

It has recently been considered that free radicals are closely involved in the pathogenesis of Parkinson's disease (PD), and the level of nitric oxide radical (N0), one of the free radicals, is reported to increase in PD brain. In the present study, we established a direct detection system for N0 in an in vitro •NO-generating system using 3-(2-hydroxy-1 -methylethyl-2-nitrosohydrazino)-N-methyl-1-propanamine as an N0 donor and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1 -oxyl 3oxide (carboxy-PTIO) by electron spin resonance (ESR) spectrometry and examined the quenching effects of the dopamine agonists pergolide and bromocriptine on the amount of N0 generated. N0 appeared to be scavenged by pergolide and, to a lesser extent, by bromocriptine. In the competition assay, the 50% inhibitory concentration values for pergolide and bromocriptine were estimated to be -23 and 200 j.tM, respectively. It was previously reported that in vivo treatment of pergolide and bromocriptine completely protected against the decrease in levels of striatal dopamine and its metabolites in the 6-hydroxydopamine-injected mouse. Considering these findings, pergolide and probably bromocriptine may also protect against dysfunction of dopaminergic neurons because of its multiple effects; not only does it stimulate the presynaptic autoreceptors, but it also directly scavenges N0 radicals and hence protects against N0related cytotoxicity. This ESR spectrometry method using carboxy-PTIO may be useful for screening other drugs that can quench N0. Key Words: Nitric oxide-Free radical-Pergolide-Dopamine agonist-Scavenging effect-2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide-Electron spin resonance.

Antiparkinsonian Drugs and Their Neuroprotective Effects.

“…3,4) Similar phenomena were observed in MPTP-treated animals used as models of parkinsonism. 27,70) Recent studies have suggested that ergot-derivative D 2 -receptor agonists, such as bromocriptine, pergolide and cabergoline, directly scavenge hydroxyl and/or nitric oxide (NO) radicals [71][72][73][74] and inhibit lipid peroxidation. 75,76) Ropinirole, a non-ergot D 2 -receptor agonist, also scavenges free radicals and suppresses lipid peroxidation.…”

Pramipexole Protects Spinal Motor Neuron Death Against Glutamate-Induced Neurotoxicity

“…Several studies have reported antioxidation or scavenging of free radicals for dopamine agonists, including apomorphine, bromocriptine, pergolide, PPX and ropinirole in cell cultures and animal model of injury of substantia nigra [14][15][16][17][18][19][20][21][22][23]. Preincubation of primary mesencephalic neuronal cultures with bromocriptine or quinpirole has provided neuroprotection against glutamate-induced neurotoxicity [24].…”

Capacities of the dopamine receptor agonist pramipexole in the treatment of patients with Parkinson’s disease

“…Антиоксидантный эффект реализуется за счет нали-чия в структуре большинства АДР гидроксилированного бензольного кольца, имеющего свойства «сборщика» сво-бодных радикалов. Многочисленные экспериментальные исследования показали, что АДР предотвращают действие митохондриальных токсинов, повышают экспрессию глута-тиона, каталазы и супероксиддисмутазы в нейронах, значи-тельно уменьшают концентрацию активных форм кислоро-да в митохондриальной фракции [11][12][13]. Свойства АДР подавлять апоптоз наиболее убедительно показаны для прамипексола.…”