A stereoselective pentobarbital binding site in cholinergic membranes from Torpedocalifornica

Miller, Keith W.; Sauter, JF; Braswell, Leon M.

doi:10.1016/0006-291x(82)91485-1

Cited by 10 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Barbiturates also affect other neurotransmitter receptors. An inhibition of radioligand binding to both nicotinic (Miller et al, 1982) and muscarinic ) acetylcholine receptors has been observed. For the nicotinic re- ceptor an allosteric mechanism has been made plausible (Dodson and Miller, 1983).…”

Section: Markmentioning

confidence: 92%

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors

Lohse

Klotz

Jakobs

et al. 1985

Journal of Neurochemistry

View full text Add to dashboard Cite

Barbiturates in pharmacologically relevant concentrations inhibit binding of (R)-N6-phenylisopropyl[3H]adenosine ([3H]PIA) to solubilized A1 adenosine receptors in a concentration-dependent, stereospecific, and competitive manner. Ki values are similar to those obtained for membrane-bound receptors and are 31 microM for (+/-)-5-(1,3-dimethyl)-5-ethylbarbituric acid [(+/-)-DMBB] and 89 microM for (+/-)-pentobarbital. Kinetic experiments demonstrate that barbiturates compete directly for the binding site of the receptor. The inhibition of rat striatal adenylate cyclase by unlabelled (R)-N6-phenylisopropyladenosine [(R)-PIA] is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A2 adenosine receptors in membranes from N1E 115 neuroblastoma cells is antagonized only by 10-30 times higher concentrations of barbiturates. It is concluded that barbiturates are selective antagonists at the A1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A1 adenosine receptor antagonism may convey excitatory properties to barbiturates.

show abstract

Section: Markmentioning

confidence: 92%

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors

Lohse

Klotz

Jakobs

et al. 1985

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…The hypothesis explains the non-linearity and variability of pressure reversal observed with some intravenous anaesthetics in mammals, although pharmacodynamic explanations have not entirely been ruled out. Several of the structurally diverse anaesthetics appear to act by specific allosteric mechanisms in addition to their effects based on lipid solubility (Olsen, 1982;Miller, Sauter & Braswell, 1982;Braswell, Dodson & Miller, 1984). However, with the simple agents used in the present work, we found highly linear pressure reversal (Fig.…”

Section: Discussionmentioning

confidence: 99%

The physiological effects of hydrostatic pressure are not equivalent to those of helium pressure on Rana pipiens.

Dodson¹,

Furmaniuk²,

Miller³

1985

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The effects of helium pressure and hydrostatic pressure on Rana pipiens were compared.2. Both agents caused paralysis at pressures greater than 135 atmospheres (1 atm = 101-325 kPa), but the median pressure for hydrostatic-pressure-induced paralysis was 35 atm less than that for helium pressure.3. When the ability of both pressurizing agents to reverse urethane-induced anaesthesia was compared, it was found that hydrostatic pressure raised the median dose for anaesthesia 2-2-fold more per atmosphere than did helium pressure.4. Animals that were lightly anaesthetized by urethane at 110 atm hydrostatic pressure became more deeply anaesthetized when helium was admitted isobarically into the pressure chamber. This difference in depth of anaesthesia between hydrostatic pressure and helium pressure is consistent with helium possessing an inherent anaesthetic effect.5. The abilities of other gases to pressure-reverse urethane anaesthesia were also determined. The degree of attenuation of the full pressure reversal effect observed with hydrostatic pressure was proportional to the lipid solubility of the gases, increasing in the order helium, neon, hydrogen, nitrogen and argon.6. Our data on the difference between hydrostatic and helium pressure are consistent with the critical volume hypothesis.

show abstract

“…7–9 Such sensitivity to small changes in barbiturate chemical structure implies there are specific barbiturate binding sites as evidenced by saturable and stereospecific binding of radiolabeled pentobarbital to nACh receptor. 10 …”

Section: Introductionmentioning

confidence: 99%

“…Although activity tends to increase with hydrophobicity, small changes in their chemical structure can radically alter action on the CNS. For example, adding a single methyl group to the general anesthetic pentobarbital (5-ethyl-5-( pentan-2-yl )pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione) produces the convulsant DMBB (5-ethyl-5-( 4-methylpentan-2-yl )pyrimidine-2,4,6(1 H ,3 H ,5 H )-trione). − Such sensitivity to small changes in barbiturate chemical structure implies there are specific barbiturate binding sites as evidenced by saturable and stereospecific binding of radiolabeled pentobarbital to nACh receptor …”

Section: Introductionmentioning

confidence: 99%

“…7−9 Such sensitivity to small changes in barbiturate chemical structure implies there are specific barbiturate binding sites as evidenced by saturable and stereospecific binding of radiolabeled pentobarbital to nACh receptor. 10 The precise location of the barbiturate binding sites on their molecular targets still remains unknown. In one study of anesthetic action, knock-in mice with a N265M mutation in the GABA A receptor β3 subunit, 11 displayed insensitivity to pentobarbital, as well as etomidate and propofol, 12 demonstrating that β3-containing GABA A receptors are responsible for anesthetic action.…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

et al. 2012

Self Cite

View full text Add to dashboard Cite

We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by x-ray crystallography. Additionally, we obtained the 3H-labeled ligand with high specific radioactivity. R-(−)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC50 approaches those for propofol and etomidate, whereas S-(+)-14 is tenfold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(−)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human α1β2/3γ2L GABAA receptors. Finally, R-(−)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both α1 and β3 subunits of human α1β3 GABAA receptors. These results indicate R-(−)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

show abstract

A stereoselective pentobarbital binding site in cholinergic membranes from Torpedocalifornica

Cited by 10 publications

References 9 publications

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors

The physiological effects of hydrostatic pressure are not equivalent to those of helium pressure on Rana pipiens.

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

Contact Info

Product

Resources

About

A stereoselective pentobarbital binding site in cholinergic membranes from Torpedocalifornica

Cited by 10 publications

References 9 publications

Barbiturates Are Selective Antagonists at A1 Adenosine Receptors

Barbiturates Are Selective Antagonists at A1 Adenosine Receptors

The physiological effects of hydrostatic pressure are not equivalent to those of helium pressure on Rana pipiens.

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

Contact Info

Product

Resources

About

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors

Barbiturates Are Selective Antagonists at A₁ Adenosine Receptors