Last update 01 Nov 2024

ADRA1 x NMDA receptor

Last update 01 Nov 2024

Basic Info

Related Targets

ADRA1NMDA receptor

Drugs associated with ADRA1 x NMDA receptor

Dextromethorphan/Guaifenesin/Phenylephrine

Target

ADRA1 x NMDA receptor

Mechanism

ADRA1 agonists [+1]

Active Org.

Everett Laboratories Inc

Originator Org.

Everett Laboratories Inc

Active Indication

Cough [+1]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Dextromethorphan/Phenylephrine

Target

ADRA1 x NMDA receptor

Mechanism

ADRA1 agonists [+1]

Active Org.

Yangzhou Sanyao Pharmaceutical Co. Ltd.

Originator Org.

Yangzhou Sanyao Pharmaceutical Co. Ltd.

Active Indication-

Inactive Indication-

Drug Highest PhaseIND Application

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ADRA1 x NMDA receptor

100 Translational Medicine associated with ADRA1 x NMDA receptor

0 Patents (Medical) associated with ADRA1 x NMDA receptor

Literatures (Medical) associated with ADRA1 x NMDA receptor

01 Jun 2022·British Journal of Clinical PharmacologyQ2 · MEDICINE

Pharmacological profile of ALKS 7119, an investigational compound evaluated for the treatment of neuropsychiatric disorders, in healthy volunteers

Q2 · MEDICINE

Article

Author: Sun, Lei ; Lin, Richard ; de Kam, Marieke L. ; von Moltke, Lisa L. ; van Gerven, Joop M. A. ; Siebenga, Pieter S. ; Leigh‐Pemberton, Richard A. ; Zuiker, Rob G. J. A. ; Rezendes, David ; Dijkstra, Francis M. ; Manthis, Joan D.

AimsALKS 7119 is a novel compound with in vitro affinity highest for the SERT, and for μ receptor, α1A‐adrenoceptor, α1B‐adrenoceptor, NMDA receptor and sigma non‐opioid intracellular receptor 1. This first‐in‐human study evaluated safety and PK/PD effects of single ascending doses (SAD) of ALKS 7119 in healthy males and compared effects with neurotransmitter modulators with partially overlapping targets.MethodsIn 10 cohorts (n = 10 subjects each), PK, safety and PD (NeuroCart tests, measuring neurophysiologic effects [pupillometry, pharmaco‐EEG (pEEG)], visuomotor coordination, alertness, [sustained] attention [saccadic peak velocity, adaptive tracking], subjective drug effects [VAS Bowdle and VAS Bond and Lader] and postural stability [body sway]) were evaluated. Neuroendocrine effects (cortisol, prolactin, growth hormone) were measured. Data were analysed over the 12‐hour post‐dose period using mixed‐effects model for repeated measure (MMRM) with baseline as covariate.ResultsALKS 7119 demonstrated linear PK and was generally well tolerated. QTcF interval increases of 30–60 ms compared to baseline were observed with ALKS 7119 doses of ≥50 mg without related adverse events. Significant increases in left and right pupil/iris ratio were observed at dose levels ≥50 mg (estimate of difference [95% CI], P‐value) (0.04 [0.01; 0.07], P < .01) and (0.06 [0.03; 0.09], P = .01), respectively. From dose levels ≥50 mg significant increases (% change) of serum cortisol (51.7 [8.4; 112.3], P = .02) and prolactin (77.9 [34.2; 135.8], P < .01) were observed.ConclusionIn line with ALKS 7119’s in vitro pharmacological profile, the clinical profile observed in this study is most comparable to SERT inhibition.

01 Oct 2009·Progress in NeurobiologyQ1 · MEDICINE

Neuroactive steroid regulation of neurotransmitter release in the CNS: Action, mechanism and possible significance

Q1 · MEDICINE

Review

Author: Zheng, Ping

Neuroactive steroids refer to steroids that are capable of regulating neuronal activities. Neuroactive steroids, synthesized either de novo in the nervous tissue or in the peripheral endocrine glands or as synthetic steroids, have exhibited numerous important modulatory effects on brain functions and brain diseases. At the cellular level, in addition to the effect on postsynaptic receptors, most neuroactive steroids, including pregnenolone, pregnenolone sulfate, progesterone, allopregnanolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone and estradiol, have modulatory effects on the release of multiple neurotransmitters like glutamate, GABA, acetylcholine, norepinephrine, dopamine and 5-HT. Many of these effects occur in the brain regions involved in learning and memory, emotion, motivation, motor and cognition. Moreover, the effects are rather complicated, maybe depending on many factors such as types of neuroactive steroids, brain regions and presynaptic functional states. The mechanisms are also complicated. Many of them involve rapid non-genomic effects on presynaptic receptors and ion channels like sigma-1 receptor, alpha(1) receptor, nicotine receptor, D1 receptor, NMDA receptor, GABA(A) receptor and L-type Ca(2+) channels. These effects have made neuroactive steroids important regulators of synaptic transmission in the central nervous system and constitute the major basis for many important actions of neuroactive steroids on brain functions and brain diseases.

10 Jul 2006·The Journal of Comparative NeurologyQ3 · MEDICINE

Localization of the mouse α1A-adrenergic receptor (AR) in the brain: α1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors

Q3 · MEDICINE

Article

Author: Paul C. Simpson ; Manoj C. Rodrigo ; Archana Jha ; Dianne M. Perez ; Robert Papay ; Dan F. Mccune ; John C. Mcgrath ; Van A. Doze ; Robert Gaivin

alpha(1)-Adrenergic receptors (ARs) are not well defined in the central nervous system. The particular cell types and areas that express these receptors are uncertain because of the lack of high avidity antibodies and selective ligands. We have developed transgenic mice that either systemically overexpress the human alpha(1A)-AR subtype fused with the enhanced green fluorescent protein (EGFP) or express the EGFP protein alone under the control of the mouse alpha(1A)-AR promoter. We confirm our transgenic model against the alpha(1A)-AR knockout mouse, which expresses the LacZ gene in place of the coding region for the alpha(1A)-AR. By using these models, we have now determined cellular localization of the alpha(1A)-AR in the brain, at the protein level. The alpha(1A)-AR or the EGFP protein is expressed prominently in neuronal cells in the cerebral cortex, hippocampus, hypothalamus, midbrain, pontine olivary nuclei, trigeminal nuclei, cerebellum, and spinal cord. The types of neurons were diverse, and the alpha(1A)-AR colocalized with markers for glutamic acid decarboxylase (GAD), gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA) receptors. Recordings from alpha(1A)-AR EGFP-expressing cells in the stratum oriens of the hippocampal CA1 region confirmed that these cells were interneurons. We could not detect expression of the alpha(1A)-AR in mature astrocytes, oligodendrocytes, or cerebral blood vessels, but we could detect the alpha(1A)-AR in oligodendrocyte progenitors. We conclude that the alpha(1A)-AR is abundant in the brain, expressed in various types of neurons, and may regulate the function of oligodendrocyte progenitors, interneurons, GABA, and NMDA receptor containing neurons.

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