Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABA < sub > A < /sub > receptor and Ca < sub > V < /sub > 2.2 channel
In this study, we have investigated the pharmacological activity and structural interaction of two novel psychoplastogens, tabernanthalog (TBG) and ibogainalog (IBG) at heterologously-expressed rat (r) and human (h) nicotinic acetylcholine receptors (nAChRs), the rα1β2γ2L γ-aminobutyric acid type A receptor (GABAAR), and the human voltage-gated N-type calcium channel (CaV2.2 channel). Both compounds inhibited the nAChRs with the following receptor selectivity: α9α10 > α7 > α3β2 ≅ α3β4, indicating that β2/β4 subunits are relatively less important for their activity. The potencies of TBG and IBG were com...
Source: Biochemical Pharmacology - April 5, 2024 Category: Drugs & Pharmacology Authors: Han-Shen Tae Marcelo O Ortells Arsalan Yousuf Sophia Q Xu Gustav Akk David J Adams Hugo R Arias Source Type: research
Vesicular monoamine transporter-2 inhibitor JPC-141 prevents methamphetamine-induced dopamine toxicity and blocks methamphetamine self-administration in rats
Biochem Pharmacol. 2024 Apr 3:116189. doi: 10.1016/j.bcp.2024.116189. Online ahead of print.ABSTRACTPrevious research has demonstrated therapeutic potential for VMAT2 inhibitors in rat models of methamphetamine use disorder. Here, we report on the neurochemical and behavioral effects of 1-(2-methoxyphenethyl)-4-phenethypiperazine (JPC-141), a novel analog of lobelane. JPC-141 potently inhibited (Ki = 52 nM) [3H]dopamine uptake by VMAT2 in striatal vesicles with 50 to 250-fold greater selectivity for VMAT2 over dopamine, norepinephrine and serotonin plasmalemma transporters. Also, JPC-141 was 57-fold more selective for inhi...
Source: Biochemical Pharmacology - April 5, 2024 Category: Drugs & Pharmacology Authors: Cassie M Chandler Justin R Nickell A George Wilson John P Culver Peter A Crooks Michael T Bardo Linda P Dwoskin Source Type: research
Targeted mutagenesis of negatively charged amino acids outlining the substrate translocation path within the human organic cation transporter 3
Biochem Pharmacol. 2024 Apr 3:116188. doi: 10.1016/j.bcp.2024.116188. Online ahead of print.ABSTRACTRecently published cryo-EM structures of human organic cation transporters of the SLC22 family revealed seven, sequentially arranged glutamic and aspartic acid residues, which may be relevant for interactions with positively charged substrates. We analyzed the functional consequences of removing those negative charges by creating D155N, E232Q, D382N, E390Q, E451Q, E459Q, and D478N mutants of OCT3. E232Q, E459Q, and D478N resulted in a lack of localization in the outer cell membrane and no relevant uptake activity. However, D...
Source: Biochemical Pharmacology - April 5, 2024 Category: Drugs & Pharmacology Authors: Kyra-Elisa Maria Redeker Sophie Schr öder Christof D ücker J ürgen Brockmöller Lukas Gebauer Source Type: research
Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABA < sub > A < /sub > receptor and Ca < sub > V < /sub > 2.2 channel
In this study, we have investigated the pharmacological activity and structural interaction of two novel psychoplastogens, tabernanthalog (TBG) and ibogainalog (IBG) at heterologously-expressed rat (r) and human (h) nicotinic acetylcholine receptors (nAChRs), the rα1β2γ2L γ-aminobutyric acid type A receptor (GABAAR), and the human voltage-gated N-type calcium channel (CaV2.2 channel). Both compounds inhibited the nAChRs with the following receptor selectivity: α9α10 > α7 > α3β2 ≅ α3β4, indicating that β2/β4 subunits are relatively less important for their activity. The potencies of TBG and IBG were com...
Source: Biochemical Pharmacology - April 5, 2024 Category: Drugs & Pharmacology Authors: Han-Shen Tae Marcelo O Ortells Arsalan Yousuf Sophia Q Xu Gustav Akk David J Adams Hugo R Arias Source Type: research
Introduction to the Special Issue "Angiotensin Receptors"
Biochem Pharmacol. 2024 Mar 31:116180. doi: 10.1016/j.bcp.2024.116180. Online ahead of print.NO ABSTRACTPMID:38565339 | DOI:10.1016/j.bcp.2024.116180 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Ralf A Benndorf Source Type: research
Introduction to the Special Issue "Angiotensin Receptors"
Biochem Pharmacol. 2024 Mar 31:116180. doi: 10.1016/j.bcp.2024.116180. Online ahead of print.NO ABSTRACTPMID:38565339 | DOI:10.1016/j.bcp.2024.116180 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Ralf A Benndorf Source Type: research
Introduction to the Special Issue "Angiotensin Receptors"
Biochem Pharmacol. 2024 Mar 31:116180. doi: 10.1016/j.bcp.2024.116180. Online ahead of print.NO ABSTRACTPMID:38565339 | DOI:10.1016/j.bcp.2024.116180 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Ralf A Benndorf Source Type: research
Influence of tumor microenvironment on the different breast cancer subtypes and applied therapies
Biochem Pharmacol. 2024 Mar 30:116178. doi: 10.1016/j.bcp.2024.116178. Online ahead of print.ABSTRACTDespite the significant improvements made in breast cancer therapy during the last decades, this disease still has increasing incidence and mortality rates. Different targets involved in general processes, like cell proliferation and survival, have become alternative therapeutic options for this disease, with some of them already used in clinic, like the CDK4/6 inhibitors for luminal A tumors treatment. Nevertheless, there is a demand for novel therapeutic strategies focused not only on tumor cells, but also on their microe...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Cristina Ferreira Almeida Georgina Correia-da-Silva Nat ércia Teixeira Cristina Amaral Source Type: research
Targeting reprogrammed metabolism as a therapeutic approach for respiratory diseases
Biochem Pharmacol. 2024 Mar 30:116187. doi: 10.1016/j.bcp.2024.116187. Online ahead of print.ABSTRACTMetabolic reprogramming underlies the etiology and pathophysiology of respiratory diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). The dysregulated cellular activities driving airway inflammation and remodelling in these diseases have reportedly been linked to aberrant shifts in energy-producing metabolic pathways: glycolysis and oxidative phosphorylation (OXPHOS). The rewiring of glycolysis and OXPHOS accompanying the therapeutic effects of many clinical compou...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Phyllis X L Gan Shanshan Zhang W S Fred Wong Source Type: research
Transcriptional control of cardiac energy metabolism in health and disease: Lessons from animal models
Biochem Pharmacol. 2024 Mar 30:116185. doi: 10.1016/j.bcp.2024.116185. Online ahead of print.ABSTRACTCardiac ATP production is tightly regulated in order to satisfy the evolving energetic requirements imposed by different cues during health and pathological conditions. In order to sustain high ATP production rates, cardiac cells are endowed with a vast mitochondrial network that is essentially acquired during the perinatal period. Nevertheless, adult cardiac cells also adapt their mitochondrial mass and oxidative function to changes in energy demand and substrate availability by fine-tuning the pathways and mitochondrial m...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Teresa Rubio-Tom ás Carolina Soler-Botija Ofelia Mart ínez-Estrada Josep A Villena Source Type: research
The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials
Biochem Pharmacol. 2024 Mar 30:116186. doi: 10.1016/j.bcp.2024.116186. Online ahead of print.ABSTRACTIschemic stroke is one of the leading causes of death and disability. Occlusion and reperfusion of cerebral blood vessels (i.e., ischemia/reperfusion (I/R) injury) generates reactive oxygen species (ROS) that contribute to brain cell death and dysfunction of the blood-brain barrier (BBB) via oxidative stress. BBB disruption influences the pathogenesis of ischemic stroke by contributing to cerebral edema, hemorrhagic transformation, and extravasation of circulating neurotoxic proteins. An improved understanding of mechanisms...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Jeffrey J Lochhead Patrick T Ronaldson Thomas P Davis Source Type: research
Influence of tumor microenvironment on the different breast cancer subtypes and applied therapies
Biochem Pharmacol. 2024 Mar 30:116178. doi: 10.1016/j.bcp.2024.116178. Online ahead of print.ABSTRACTDespite the significant improvements made in breast cancer therapy during the last decades, this disease still has increasing incidence and mortality rates. Different targets involved in general processes, like cell proliferation and survival, have become alternative therapeutic options for this disease, with some of them already used in clinic, like the CDK4/6 inhibitors for luminal A tumors treatment. Nevertheless, there is a demand for novel therapeutic strategies focused not only on tumor cells, but also on their microe...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Cristina Ferreira Almeida Georgina Correia-da-Silva Nat ércia Teixeira Cristina Amaral Source Type: research
Targeting reprogrammed metabolism as a therapeutic approach for respiratory diseases
Biochem Pharmacol. 2024 Mar 30:116187. doi: 10.1016/j.bcp.2024.116187. Online ahead of print.ABSTRACTMetabolic reprogramming underlies the etiology and pathophysiology of respiratory diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). The dysregulated cellular activities driving airway inflammation and remodelling in these diseases have reportedly been linked to aberrant shifts in energy-producing metabolic pathways: glycolysis and oxidative phosphorylation (OXPHOS). The rewiring of glycolysis and OXPHOS accompanying the therapeutic effects of many clinical compou...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Phyllis X L Gan Shanshan Zhang W S Fred Wong Source Type: research
Transcriptional control of cardiac energy metabolism in health and disease: Lessons from animal models
Biochem Pharmacol. 2024 Mar 30:116185. doi: 10.1016/j.bcp.2024.116185. Online ahead of print.ABSTRACTCardiac ATP production is tightly regulated in order to satisfy the evolving energetic requirements imposed by different cues during health and pathological conditions. In order to sustain high ATP production rates, cardiac cells are endowed with a vast mitochondrial network that is essentially acquired during the perinatal period. Nevertheless, adult cardiac cells also adapt their mitochondrial mass and oxidative function to changes in energy demand and substrate availability by fine-tuning the pathways and mitochondrial m...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Teresa Rubio-Tom ás Carolina Soler-Botija Ofelia Mart ínez-Estrada Josep A Villena Source Type: research
The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials
Biochem Pharmacol. 2024 Mar 30:116186. doi: 10.1016/j.bcp.2024.116186. Online ahead of print.ABSTRACTIschemic stroke is one of the leading causes of death and disability. Occlusion and reperfusion of cerebral blood vessels (i.e., ischemia/reperfusion (I/R) injury) generates reactive oxygen species (ROS) that contribute to brain cell death and dysfunction of the blood-brain barrier (BBB) via oxidative stress. BBB disruption influences the pathogenesis of ischemic stroke by contributing to cerebral edema, hemorrhagic transformation, and extravasation of circulating neurotoxic proteins. An improved understanding of mechanisms...
Source: Biochemical Pharmacology - April 1, 2024 Category: Drugs & Pharmacology Authors: Jeffrey J Lochhead Patrick T Ronaldson Thomas P Davis Source Type: research
