Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain

1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic® surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution—alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations.

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Pharmacologically and Functionally Distinct Calcium Currents of Stomatogastric Neurons

Journal of Neurophysiology ◽

10.1152/jn.1998.79.4.2070 ◽

1998 ◽

Vol 79 (4) ◽

pp. 2070-2081 ◽

Cited By ~ 10

Author(s):

Laura M. Hurley ◽

Katherine Graubard

Keyword(s):

Neuromuscular Junction ◽

Calcium Channel ◽

Calcium Current ◽

Calcium Influx ◽

Outward Current ◽

Calcium Currents ◽

High Threshold ◽

Channel Blockers ◽

Postsynaptic Potentials ◽

Different Types

Hurley, Laura M. and Katherine Graubard. Pharmacologically and functionally distinct calcium currents of stomatogastric neurons. J. Neurophysiol. 79: 2070–2081, 1998. Previous studies have suggested the presence of different types of calcium channels in different regions of stomatogastric neurons. We sought to pharmacologically separate these calcium channel types. We used two different preparations from different regions of stomatogastric neurons to screen a range of selective calcium channel blockers. The two preparations were isolated cell bodies in culture, in which calcium current was measured directly, and isolated neuromuscular junction, in which synaptic transmission was the indirect assay for presynaptic calcium influx. The selective blockers were two different dihydropyridines, ω-Agatoxin IVA, and ω-Conotoxin GVIA. Cultured cell bodies possessed both high-threshold calcium current and calcium-activated outward current, similar to intact neurons. The calcium current had transient and maintained components, but both components had the same voltage dependence of activation and inactivation. Dihydropyridines at ≥10 μM blocked both high-threshold calcium current and calcium-activated outward current. Nanomolar doses of ω-Agatoxin IVA did not block calcium current, but micromolar doses did. ω-Conotoxin GVIA did not block either current. In contrast, at the neuromuscular junction, dihydropyridines reduced the amplitude of postsynaptic potentials by only a modest amount, whereas ω-Agatoxin IVA at doses as low as 64 nM reduced the amplitude of postsynaptic potentials almost entirely. These effects were presynaptic. ω-Conotoxin GVIA did not change the amplitude of postsynaptic potentials. The different pharmacological profiles of the two isolated preparations suggest that there are at least two different types of calcium channel in stomatogastric neurons and that ω-Agatoxin IVA and dihydropridines can be used to pharmacologically distinguish them.

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A Systematic Review on 1, 4-Dihydropyridines and its Analogues: An Elite Scaffold

Biointerface Research in Applied Chemistry ◽

10.33263/briac123.31173134 ◽

2021 ◽

Vol 12 (3) ◽

pp. 3117-3134

Keyword(s):

Myocardial Infarction ◽

Systematic Review ◽

Clinical Trials ◽

Calcium Channels ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Calcium Influx ◽

Channel Blockers ◽

Neuroprotective Effects ◽

Dihydropyridine Derivatives

1,4-Dihydropyridines are a group of pyridine-based molecules possessing a magnificent set of biological and therapeutic potentials. Belonging to the class of calcium channel blockers, they are known to be effective in the conditions, angina, hypertension, myocardial infarction and show vasodilatory and cardiac depressant effects. Hypotensive, antimicrobial, anticancer, anticoagulant, antioxidant, anticonvulsant, antimalarial, antiulcer, and neuroprotective effects have been reported with their rational use. The effects are precipitated in response to inhibition of calcium channels, gradually restricting calcium influx. Drugs like nifedipine, felodipine, and amlodipine are commonly used clinically. Several other drugs belonging to this class have been under clinical trials. The present review focuses on the various 1,4-dihydropyridine derivatives and their pharmacological actions.

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