Nimodipine Enhancement of α2 Adrenergic Modulation of NMDA Receptor via a Mechanism Independent of Ca²⁺Channel Blocking

Abstract

These in vitro and in vivo findings demonstrate a novel neural mechanism involving nimodipine enhancement of alpha2 signaling in RGCs. This nimodipine effect appears to be independent of its classic L-type Ca(2+) channel-blocking action.

Neural Mechanisms Underlying Brimonidine’s Protection of Retinal Ganglion Cells in Experimental Glaucoma

“…However, in the retina the L-type Ca ++ channel plays a dominant role in transmitter release, particularly at photoreceptor and bipolar cell synaptic terminals where glutamate is released (Morgans et al, 2005;Pan, 2000Pan, , 2001Tachibana et al, 1993). Using several commonly used L-type Ca ++ channel blockers, we demonstrated that the depolarization (using a high K+ Ringer) induced Ca ++ signals at IPL were mediated predominantly by the L-type Ca ++ channel (Dong et al, 2010; see also Fig. 12B & 12C).…”

“…In the rabbit retinal ganglion cell layer, approximately two-thirds of the neurons are RGCs and the remaining one-third are displaced amacrine cells, predominantly displaced starburst amacrine cells (dsACs, 85% of all displace amacrine cells, Vaney, 1984;Vaney et al, 1981). These dsACs can be selectively labeled with a very low dose of DAPI (4',6-diamidino-2-phenylindole, a fluorescent nuclear dye, Vaney et al, 1981;Dong et al, 2010). We found that these dsACs are resistant to NMDA excitotoxicity: the same intravitreal dose of NMDA (3.6 μmol) that produced a substantial cell loss at ganglion cell layer had no effect on dsACs (Fig.…”

Autonomic Regulation of the Function of the Vitreous Body and Retina

“…Presence of adrenergic receptors on membranes [11,12] is shown. Highly selective agonist α2adrenoreceptor brimonidine with local administration is in the vitreous body and aqueous fluid of the human eye [13].…”

Searching for calcium antagonists for hypertension disease therapy from Moutan Cortex, using bioactivity integrated UHPLC‐QTOF‐MS

“…The calcium channels are mainly divided into voltage‐operated calcium ion (Ca 2+ ) channels (VOCCs), inositol 1,4,5‐trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) . Clinically, most calcium channel blockers act by antagonising L‐VOCCs (L‐type), and there are three main types of blockers: dihydropyridines, phenylalkylamine and benzothiazepines . However, the existing CCBs inevitably induce some adverse reactions, such as frequent micturition, bradycardia, headaches and lung cancer, and exceed the access and/or affordability of the majority of the world's population who are looking for alternative treatments …”