Deprotonation Dynamics of Local Anesthetics in Hydrophobic Media: Dibucainehci in Water/Alcohol or Surfactant Mixtures

Lin, C. T.; Williamson, L. Neil; Chyan, Y. G.; Marques, Alberto

doi:10.1111/j.1751-1097.1988.tb02888.x

Cited by 11 publications

(11 citation statements)

References 17 publications

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“…The results revealed that the photophysical properties of free base, hydrogen-bonded and protonated dibucaines are quite unique and distinguishable from one another. These properties were used to probe the deprotonation of dibucaine.HC1 in the waterihydrophobic media (Lin et al, 1988). The second aspect is the characterization of the action sites and action mechanisms by the incorporation of drug species in the membrane.…”

Section: Tatracaine Proaimmentioning

confidence: 99%

PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS

Mertz

Marques

Williamson

et al. 1990

Photochem & Photobiology

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The effects of solvent and concentration on the photophysical properties of tertiary amine local anesthetics, tetracaine and procaine were studied experimentally using low temperature (77 K) emission spectroscopy and confirmed theoretically using a HAM/3 method. For tetracaine free base in methylcyclohexane, a broad fluorescence band observed at approximately 375 nm for concentrations greater than 1 x 10(-3) M is assigned to the molecular self-associated species. The disappearance of this band in ethanol (i.e. a model hydrophobic environment) indicates a greater tendency of neutral tetracaine towards molecular hetero-association. In an aqueous solution of procaine.HCl, a broad emission band centered at approximately 400 nm is detected even at a concentration as low as 1 x 10(-4) M and is attributed to the charged aggregates of procaine.HCl. Two general observations for procaine, tetracaine and dibucaine are noted: (1) the monocation and free base local anesthetics in ethanol solutions give identical photophysical properties, suggesting that the monocation drug species in ethanol is H+ dissociative, and (2) the lowest singlet excited state of neutral local anesthetics is calculated to have a charge-transfer character originating from a non-bonding electron in the N of tertiary amine group to the pi orbital of aromatic ring. The possible pharmacological implications of the deprotonation, the drug aggregations and the charge-transfer excitations of local anesthetics on the molecular basis of anesthesia are discussed.

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Section: Tatracaine Proaimmentioning

confidence: 99%

PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS

Mertz

Marques

Williamson

et al. 1990

Photochem & Photobiology

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“…Deprotonation of dibucaine occurred when the amine was brought in contact with lipophilic environments (Lin et al 1988). Based on the commonly used interpretation of 9-AA fluorescence signals (Schuldiner et al 1972), further evidence against 'classical' amine-type uncoupling by dibucaine comes from the observation that ApH inhibition was not dependent on the strength of ApH (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the transthylakoid gradient of electrochemical proton potential by the local anesthetic dibucaine

Laasch

Schumann

Günther

1991

Planta

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The effects of the local anesthetic dibucaine on coupling between electron transport and ATP synthesis-hydrolysis by the coupling-factor complex (CF0CF1 ATPase) were investigated in thylakoid membranes from Spinacia oleracea L. cv. Monatol. Evidence is presented that inhibition of ATP synthesis was produced by a specific uncoupling mechanism which was based on dibucaine-membrane surface interactions rather than on the interaction of dibucaine with the ATPase complex. Dibucaine reduced the osmotic space of thylakoid vesicles. At low pH of the medium it stimulated ATP hydrolysis beyond the rates obtained with optimum concentrations of 'classical' uncouplers. After addition of dibucaine, there was displacement of membrane-bound Mg(2+) and strong thylakoid stacking in the presence of only low Mg(2+) concentrations. Inhibition of ATP synthesis and transmembrane pH gradient increased with medium pH. Hydrolysis of ATP by isolated CF1 and the CF0CF1 complex was only slightly affected by dibucaine. The data are discussed assuming the involvement of localized proton channels on the membrane surface in protonic coupling of electron transport and ATP synthesis. A hypothesis for the mechanisms of action of local anesthetics at the thylakoid membrane is presented.

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“…3 -6 The experimental set-up for recording the fluorescence and phosphorescence spectra and lifetimes at 77 K has also been described elsewhere. 4 …”

Section: Methodsmentioning

confidence: 97%

“…3 . 4 These offer as viable 'direct' emission probes for studying the nature of their solubilizing microenvironment in sol-gel matrix.…”

Section: Introductionmentioning

confidence: 99%

Evidence of Modifications of Micellar Interface In Sol-Gel Glass

Catuara

Lin

1994

MRS Proc.

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A new sol-gel procedure using micellar solutions has been developed to immobilize local anesthetic drugs in optically transparent glass. Dibucaine was selected as a direct emission probe at 77 K for determining the forms of the anesthetic drug (free base, monoprotonated, and/or diprotonated) and its location (hydrophobic core, interfacial layer or hydrophilic region) in micelles. The photophysical properties of local anesthetics obtained in gels are compared to those in solutions. During the gelation stage, the predominant drug species was identified as free base dibucaine embedded in the hydrophobic core of neutral as well as charged micelles. This observation suggests that the micellar interface was modified by the large hydrophilic gel surface during the gelation stage. The modified micellar interface allows an increase in the partition of free base dibucaine into the hydrophobic region. At the xerogel stage, however, the collapse of micellar structure provides a direct interaction of dibucaine with the acidic gel surface, leading to a formation of diprotonated dibucaine. The results are discussed in terms of molecular basis of pharmacological implications such as drug delivery, release, and transport under microencapsulation conditions.

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Deprotonation Dynamics of Local Anesthetics in Hydrophobic Media: Dibucainehci in Water/Alcohol or Surfactant Mixtures

Cited by 11 publications

References 17 publications

PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS

PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS

Inhibition of the transthylakoid gradient of electrochemical proton potential by the local anesthetic dibucaine

Evidence of Modifications of Micellar Interface In Sol-Gel Glass

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