Phenmetrazine Hydrochloride

Phenmetrazine hydrochloride acts as a substrate at norepinephrine and dopamine transporters, producing concentration-dependent release of these monoamines from presynaptic terminals. Acute administration of phenmetrazine at 50 mg/kg significantly increases local cerebral glucose utilization in basal ganglia and motor-related brain regions, as measured by 2-[14C]-deoxyglucose uptake. Chronic phenmetrazine treatment dose-dependently attenuates D2 dopamine receptor and α2-adrenergic receptor-mediated G-protein activation, as determined by [35S]GTPγS binding assays, while 5-HT1A receptor activity remains unaffected. Two distinct patterns of phosphorylation changes are observed following phenmetrazine exposure: chronic low-dose treatment decreases phosphorylated ERK1/2 levels and increases phosphorylated DARPP-32 in select regions, whereas acute and chronic high-dose treatment elevate pERK1/2 levels but reduce pDARPP-32. Chronic low-dose phenmetrazine also significantly reduces phosphorylated GSK3β levels in several brain regions.

Fig. 1 Fluorescence image of rat brain sections following phenmetrazine treatment. (Keegan B M.; et al. 2021)