N6-Cycloalkyl- andN6-Bicycloalkyl-C5′(C2′)-modified Adenosine Derivatives as High-Affinity and Selective Agonists at the Human A1Adenosine Receptor with Antinociceptive Effects in Mice

2009 ◽  
Vol 52 (8) ◽  
pp. 2393-2406 ◽  
Author(s):  
Palmarisa Franchetti ◽  
Loredana Cappellacci ◽  
Patrizia Vita ◽  
Riccardo Petrelli ◽  
Antonio Lavecchia ◽  
...  
Keyword(s):  
High Affinity ◽  
Antinociceptive Effects ◽  
Adenosine Derivatives ◽  
Selective Agonists

scholarly journals N6-Cycloalkyl- andN6-Bicycloalkyl-C5′(C2′)-modified Adenosine Derivatives as High-Affinity and Selective Agonists at the Human A1Adenosine Receptor with Antinociceptive Effects in Mice

2009 ◽  
Vol 52 (10) ◽  
pp. 3430-3430 ◽  
Author(s):  
Palmarisa Franchetti ◽  
Loredana Cappellacci ◽  
Patrizia Vita ◽  
Riccardo Petrelli ◽  
Antonio Lavecchia ◽  
...  
Keyword(s):  
High Affinity ◽  
Antinociceptive Effects ◽  
Adenosine Derivatives ◽  
Selective Agonists

Design and Synthesis of a Series of 6-Substituted-2-pyridinylmethylamine Derivatives as Novel, High-Affinity, Selective Agonists at 5-HT1AReceptors

1998 ◽  
Vol 41 (25) ◽  
pp. 5070-5083 ◽  
Author(s):  
Bernard Vacher ◽  
Bernard Bonnaud ◽  
Philippe Funes ◽  
Nathalie Jubault ◽  
Wouter Koek ◽  
...  
Keyword(s):  
Design And Synthesis ◽  
High Affinity ◽  
Selective Agonists

Both CCK-A and CCK-B/gastrin receptors are present on rabbit vagus nerve

1992 ◽  
Vol 263 (3) ◽  
pp. R591-R595 ◽  
Author(s):  
C. W. Lin ◽  
T. R. Miller
Keyword(s):  
Vagus Nerve ◽  
Receptor Site ◽  
Vagal Afferents ◽  
Scatchard Analysis ◽  
Vagus Nerves ◽  
Binding Studies ◽  
Cck Receptors ◽  
High Affinity ◽  
Selective Agonists ◽  
Subtype Selective

Cholecystokinin (CCK) receptors on vagal afferents have been implicated in many of the actions of the brain-gut peptide CCK, including satiety. Autoradiographic studies in rats have demonstrated the presence of CCK-A-type receptors on vagus nerves. However, direct and detailed characterization of this important CCK receptor site has never been reported with membrane-binding techniques. Using 125I-Bolt-on-Hunter-CCK octapeptide (125I-BH-CCK-8) and the recently discovered selective agonists and antagonists of CCK receptors, we have delineated the properties of CCK receptors on rabbit vagus nerve. 125I-BH-CCK-8 binding sites appeared to be homogeneous by the Scatchard analysis, with a dissociation constant of 0.14 nM and a maximum binding of 72 fmol/mg protein. However, competition studies using selective CCK ligands showed that the vagal CCK receptors are heterogeneous. A71378, a selective CCK-A agonist, showed biphasic displacement curves, with the high-affinity portion (less than 10 nM) accounting for approximately 60% and the low-affinity portion for approximately 40%. Competitive binding studies using A63387, a selective CCK-B/gastrin receptor agonist, also showed biphasic displacement curves, with the high-affinity portion (less than 30 nM) at approximately 40% and the low-affinity portion at approximately 60%. Under conditions which selectively examined vagal CCK-A or CCK-B/gastrin receptors, we demonstrated that a number of CCK subtype selective agonists and antagonists possessed similar affinities for the vagal CCK-A and -B/gastrin receptors as those found on the guinea pig pancreas (CCK-A) and cerebral cortex (CCK-B), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Adrenoceptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Katrin Altosaar ◽  
Poornima Balaji ◽  
Richard A. Bond ◽  
David B. Bylund ◽  
Susanna Cotecchia ◽  
...  
Keyword(s):  
Cardiac Failure ◽  
Species Variation ◽  
Baroreflex Control ◽  
Α2 Adrenoceptors ◽  
Adrenoceptor Antagonist ◽  
High Affinity ◽  
Selective Antagonists ◽  
Α2 Adrenoceptor ◽  
Adrenoceptor Agonists ◽  
Selective Agonists

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [58], see also [180]. Adrenoceptors, α1α1-Adrenoceptors are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. phenylephrine, methoxamine and cirazoline are agonists and prazosin and cirazoline antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy PLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. Selective α1-adrenoceptor agonists are used as nasal decongestants; antagonists to treat hypertension (doxazosin, prazosin) and benign prostatic hyperplasia (alfuzosin, tamsulosin). The α1- and β2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of α1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are α1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension and extrapyramidal effects.Adrenoceptors, α2 α2-Adrenoceptors are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine and talipexole are agonists and rauwolscine and yohimbine antagonists selective for α2- relative to α1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine and [3H]RX821002 are relatively selective radioligands. There is species variation in the pharmacology of the α2A-adrenoceptor. Multiple mutations of α2-adrenoceptors have been described, some associated with alterations in function. Presynaptic α2-adrenoceptors regulate many functions in the nervous system. The α2-adrenoceptor agonists clonidine, guanabenz and brimonidine affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is used as a sedative and analgesic in human and veterinary medicine with sympatholytic and anxiolytic properties. The α2-adrenoceptor antagonist yohimbine has been used to treat erectile dysfunction and mirtazapine as an anti-depressant. The α2B subtype appears to be involved in neurotransmission in the spinal cord and α2C in regulating catecholamine release from adrenal chromaffin cells.Adrenoceptors, ββ-Adrenoceptors are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for β-adrenoceptors relative to α1- and α2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively β1 and β2 adrenoceptor-selective antagonists. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for β1- relative to β2-adrenoceptors. Pharmacological differences exist between human and mouse β3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human β3-adrenoceptor whereas CGP 12177 and L 755507 activate human β3-adrenoceptors [88]. β3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at β3-adrenoceptors, but does not discriminate well between the three β- subtypes whereas L 755507 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label β1- and β2- adrenoceptors and β3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with β1- and β2-adrenoceptor antagonists. [3H]-L-748337 is a β3-selective radioligand [474]. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track β-adrenoceptors at the cellular level [8]. Somewhat selective β1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. β1-Adrenoceptor-preferring antagonists are used to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol), cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol). Cardiac failure is also treated with carvedilol that blocks β1- and β2-adrenoceptors, as well as α1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting β2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation β-adrenoceptor antagonists (propranolol) block both β1- and β2-adrenoceptors and there are no β2-adrenoceptor-selective antagonists used therapeutically. The β3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome.

RP 60180 : A novel phenothiazine with high affinity for kappa binding sites and with antinociceptive effects in rodents

Pain ◽  
1990 ◽  
Vol 41 ◽  
pp. S192 ◽  
Author(s):  
V. Fardin ◽  
B. Plau ◽  
A. Carruette ◽  
C. Guyon ◽  
T. Bardon ◽  
...  
Keyword(s):  
Binding Sites ◽  
High Affinity ◽  
Antinociceptive Effects

Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: Optimization of in vitro activity

2010 ◽  
Vol 20 (18) ◽  
pp. 5426-5430 ◽  
Author(s):  
Jens-Uwe Peters ◽  
Holger Kühne ◽  
Henrietta Dehmlow ◽  
Uwe Grether ◽  
Aurelia Conte ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
High Affinity ◽  
Selective Agonists

scholarly journals Phenyliminoimidazolidine Derivatives Activate Both Octopamine1 and Octopamine2 Receptor Subtypes in Locust Skeletal Muscle

1987 ◽  
Vol 129 (1) ◽  
pp. 239-250
Author(s):  
PETER D. EVANS
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Receptor Subtypes ◽  
High Affinity ◽  
Octopamine Receptors ◽  
Octopamine Receptor ◽  
Selective Agonists ◽  
Relative Potencies ◽  
Neuromuscular Preparation

1. The actions of the phenyliminoimidazolidine derivatives, NC7 and NC5 on octopamine receptors in the extensor-tibiae neuromuscular preparation of the locust are described. 2. The derivatives activate both OCTOPAMINE1 and OCTOPAMINE2 receptors in this preparation. They are not selective agonists of OCTOPAMINE2 receptors that activate adenylate cyclase. 3. The relative potencies of NC5 and NC7 on OCTOPAMINE1 and OCTOPAMINE2 receptors differ, suggesting that they may be useful in the development of selective agonists that can distinguish between the different pharmacological subclasses of octopamine receptor. 4. The octopamine-mediated increases in cyclic AMP levels in this preparation can be separated into high- and low-affinity components. NC5 and NC7 appear to activate the high-affinity component of this response selectively.

Convergent functional groups. 13. High-affinity complexation of adenosine derivatives within induced binding pockets

1993 ◽  
Vol 115 (9) ◽  
pp. 3548-3557 ◽  
Author(s):  
M. Morgan Conn ◽  
Ghislain Deslongchamps ◽  
Javier de Mendoza ◽  
Julius Rebek
Keyword(s):  
Functional Groups ◽  
High Affinity ◽  
Binding Pockets ◽  
Adenosine Derivatives

scholarly journals Adrenoceptors in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Katrin Altosaar ◽  
Poornima Balaji ◽  
Richard A. Bond ◽  
David B. Bylund ◽  
Susanna Cotecchia ◽  
...  
Keyword(s):  
Cardiac Failure ◽  
Baroreflex Control ◽  
Α2 Adrenoceptors ◽  
Adrenoceptor Antagonist ◽  
High Affinity ◽  
Selective Antagonists ◽  
Α2 Adrenoceptor ◽  
Nasal Decongestants ◽  
Adrenoceptor Agonists ◽  
Selective Agonists

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [60, 186]. Adrenoceptors, α1 The three α1-adrenoceptor subtypes α1A, α1B and α1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. α1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being α1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to a lesser extent hypertension (doxazosin, terazosin). The α1- and β2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of α1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are α1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension. Adrenoceptors, α2 The three α2-adrenoceptor subtypes α2A, α2B and α2C are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine and talipexole are agonists and rauwolscine and yohimbine antagonists selective for α2- relative to α1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine and [3H]RX821002 are relatively selective radioligands. There are species variations in the pharmacology of the α2A-adrenoceptor. Multiple mutations of α2-adrenoceptors have been described, some associated with alterations in function. Presynaptic α2-adrenoceptors regulate many functions in the nervous system. The α2-adrenoceptor agonists clonidine, guanabenz and brimonidine affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive (relatively little used) and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is increasingly used as a sedative and analgesic in human [31] and veterinary medicine and has sympatholytic and anxiolytic properties. The α2-adrenoceptor antagonist mirtazapine is used as an anti-depressant. The α2B subtype appears to be involved in neurotransmission in the spinal cord and α2C in regulating catecholamine release from adrenal chromaffin cells. Although subtype-selective antagonists have been developed, none are used clinically and they remain experimental tools. Adrenoceptors, β The three β-adrenoceptor subtypes β1, β2 and β3 are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for β-adrenoceptors relative to α1- and α2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively selective antagonists for β1- and β2- relative to β3-adrenoceptors. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for β1- relative to β2-adrenoceptors. Pharmacological differences exist between human and mouse β3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human β3-adrenoceptor whereas CGP 12177 (low potency) and L 755507 activate human β3-adrenoceptors [88]. β3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at β3-adrenoceptors, but does not discriminate between the three β- subtypes [320] whereas L-748337 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label β1- and β2- adrenoceptors and β3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with β1- and β2-adrenoceptor antagonists. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track β-adrenoceptors at the cellular level [8]. Somewhat selective β1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. β1-Adrenoceptor-preferring antagonists are used to treat cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol) but also in combination with other treatments to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol) [507]. Cardiac failure is also treated with carvedilol that blocks β1- and β2-adrenoceptors, as well as α1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting β2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation β-adrenoceptor antagonists (propranolol) block both β1- and β2-adrenoceptors and there are no β2-adrenoceptor-selective antagonists used therapeutically. The β3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome. There is evidence to suggest that β-adrenoceptor antagonists can reduce metastasis in certain types of cancer [189].

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