The crystal structure of lidocaine hydrochloride monohydrate

Hanson, A. W.; Röhrl, M.

doi:10.1107/s0567740872008350

Cited by 31 publications

(24 citation statements)

References 2 publications

(3 reference statements)

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“…Thus, the modeling studies were conducted on the protonated cationic form. Models were constructed by fragments, assuming the starting geometry to be similar to that found for lidocaine hydrochloride monohydrate crystal structure (Hanson and Röhrl, 1972). Equilibrium geometries were calculated starting with a systematic conformer distribution analysis.…”

Section: Methodsmentioning

confidence: 99%

Optimal Requirements for High Affinity and Use-Dependent Block of Skeletal Muscle Sodium Channel by N-Benzyl Analogs of Tocainide-Like Compounds

Talon²,

Bellis³

et al. 2003

Mol Pharmacol

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Newly synthesized tocainide analogs were tested for their state-dependent affinity and use-dependent behavior on sodium currents (I Na ) of adult skeletal muscle fibers by means of the Vaseline-gap voltage clamp method. The drugs had the pharmacophore amino group constrained in position ␣ [N-(2,6-dimethylphenyl)pyrrolidine-2-carboxamide (To5)] or ␤ [N-(2,6-dimethylphenyl)pyrrolidine-3-carboxamide (To9)] in a prolinelike cycle and/or linked to a lipophilic benzyl moiety as in N-benzyl-tocainide (Benzyl-Toc), 1-benzyl-To5 (Benzyl-To5), and 1-benzyl-To9 (Benzyl-To9). I Na were elicited with pulses to Ϫ20 mV from different holding potentials (Ϫ140, Ϫ100, and Ϫ70 mV) and stimulation frequencies (2 and 10 Hz). All compounds were voltage-dependent and use-dependent channel blockers. The presence of a proline-like cycle increased the potency; i.e., To5 was 3-and 10-fold more effective than Toc in blocking I Na at the holding potential of Ϫ140 and Ϫ70 mV, respectively. The benzyl group on the amine further enhanced drug effectiveness with the following scale: Benzyl-To9 Ն Benzyl-Toc Ͼ Benzyl-To5. At a holding potential of Ϫ100 mV and 10-Hz stimulation, Benzyl-To9 blocked I Na with a half-maximal concentration of 0.5 M, being 60 and 400 times more potent than To9 and Toc, respectively. The similar effectiveness of Benzyl-Toc and Benzyl-To9 was paralleled by a similar spatial arrangement by equilibrium geometry modeling. In addition, the latter had a higher pK a value that probably contributed to a slow kinetic during its high use-dependent behavior. Benzyl-To5 had its lowest energy level at a more folded conformation that justifies the less favorable profile among the N-benzylated analogs. The new compounds are the most potent tocainide-like sodium channel blockers so far described and have high therapeutic potentials.The block of voltage-gated Na ϩ channel by local anestheticlike (LA) drugs has therapeutic value for numerous disorders characterized by abnormal membrane excitability (Clare et al., 2000). Different channel types show different sensitivities to LAs; however, the structural basis for this difference is still poorly understood (Wang et al., 1996;Li et al., 1999;2002). The selective activity on tissue displaying abnormal excitability pattern is based on the state-dependence of LA effect (i.e., a stronger potency at depolarized membrane potential or during high frequency trains of channel activity) (Catterall, 2002). This effect is related to drug interaction with a receptor whose affinity for ligands changes with the state-dependent transitions of the channel, the affinity being the highest when the channels open or inactivate. Mutagenesis studies identified various amino acid residues, localized in the S6 segments of each homologous domain of the ␣ subunit, as critical for LA binding and activity on Na ϩ channels of various excitable tissues (Ragsdale et al., 1994(Ragsdale et al., , 1996Wright et al., 1998;Li et al., 1999;Nau et al., 1999;Wang et al., 2000;Yarov-Yarovoy et al., 2001, 2002. LAs may int...

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Section: Methodsmentioning

confidence: 99%

Optimal Requirements for High Affinity and Use-Dependent Block of Skeletal Muscle Sodium Channel by N-Benzyl Analogs of Tocainide-Like Compounds

Talon²,

Bellis³

et al. 2003

Mol Pharmacol

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“…There are at least two fundamental reasons to justify this selection. Firstly, in X-ray investigations combined with the recent dielectric studies of lidocaine hydrochloride salt, 21 it was argued that lidocaine cations tend to link to each other forming strongly hydrogen bonded chains, 32 an excellent network for fast proton hopping. Secondly, we have found that under appropriate conditions the lidocaine molecule is able to undergo an intramolecular proton transfer reaction and consequently to exist as a mixture of two easily interconvertible constitutional isomers.…”

Section: Generalmentioning

confidence: 99%

Molecular Origin of Enhanced Proton Conductivity in Anhydrous Ionic Systems

et al. 2015

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Ionic systems with enhanced proton conductivity are widely viewed as promising electrolytes in fuel cells and batteries. Nevertheless, a major challenge toward their commercial applications is determination of the factors controlling the fast proton hopping in anhydrous conditions. To address this issue, we have studied novel proton-conducting materials formed via a chemical reaction of lidocaine base with a series of acids characterized by a various number of proton-active sites. From ambient and high pressure experimental data, we have found that there are fundamental differences in the conducting properties of the examined salts.On the other hand, DFT calculations revealed that the internal proton hopping within the cation structure strongly affects the pathways of mobility of the charge carrier. These findings offer a 2 fresh look on the Grotthuss-type mechanism in protic ionic glasses as well as provide new ideas for the design of anhydrous materials with exceptionally high proton conductivity.

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“…16) Thus IDM and LDC would interact at a 2 : 1 molar ratio when dissolved in organic solvent at higher concentration than that of aqueous solution. In this case, LDC molecules formed a novel hydrogen bond network which was different from that of both LDC free form 17) and its hydrochloride monohydrate 18) as shown in Fig. 5.…”

mentioning

confidence: 99%

Molecular Complex Consisting of Two Typical External Medicines: Intermolecular Interaction between Indomethacin and Lidocaine

Umeda

Fukami

Furuishi

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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Molecular complexes have been studied to improve the physico-chemical properties of drugs for the past half century. Higuchi et al. reported that caffeine formed complexes with benzoic acid and various benzoate derivative esters in solution.1) They attempted the first quantitative evaluation regarding the molecular association responsible for the existence of these complexes and the effect on chemical stability. The complexation of some local anesthetic esters such as benzocaine,2) procaine, 3) and lidocaine 4) (LDC) with caffeine was also attempted to inhibit the hydrolysis of the ester group on these drugs in aqueous solution. To improve chemical stability and/or increase solubility, such molecular coupling, which is not covalent bonding, has been extensively investigated, for example, riboflavin-nicotinamide, 5) ampicillin-benzaldehyde, 6) and iodine-polyvinyl pyrrolidone. 7)Indomethacin (IDM), a non-steroidal anti-inflammatory drug (NSAID), has been widely used to treat tendovaginitis, arthritis, and muscle pain as an ointment, cream, gel and adhesive plaster. Since IDM is, however, practically insoluble (ca. 2.5 mg/ml) in water, cyclodextrins, 8,9) poly(amidoamine) dendrimers, 10) and several additives 11) have been utilized to improve its dissolution. Furthermore, skin permeation of IDM was enhanced by the complexation of additives with L-menthol 12) or smectite. 13)LDC topical systems are used to relieve the pain and discomfort associated with herpes zoster virus infections of the skin. Our previous study using Neurometer ® demonstrated that the application of a 9% LDC ointment decreased sensory nerve function in 12 volunteers. Nevertheless, pain relief was not achieved efficiently, because the hydrochloride salt of LDC did not sufficiently penetrate the skin tissue.14) Accordingly, the LDC ointment was reformulated by adding IDM which was expected to heal the inflamed region, because there is no commercially available external medicine consisting of LDC and IDM. In a preliminary study, we obtained a reconstituted viscous paste from IDM and LDC kneaded with an appropriate amount of water.In this study, the intermolecular interaction between IDM and LDC was examined and the formation of a complex was confirmed using thermal analysis, a polarized microscope with a hot stage, fast-atom bombardment (FAB)-MS, phasesolubility techniques, IR, and 1 H-NMR. Finally, the molecular structure of the novel complex in aqueous solution was estimated. ExperimentalMaterials IDM and LDC were of reagent grade and purchased from Wako Pure Chemical Industries Ltd. (Osaka, Japan). All other chemicals and solvents were of reagent grade and used without further purification.Preparation of the IDM and LDC Complex An equimolar mixture of IDM and LDC was kneaded with an appropriate amount of distilled water using an agate mortar and pestle for 20 min. Then the milled mixture was dried at room temperature under reduced pressure overnight.Determination of IDM and LDC IDM, LDC, and the kneaded mixture were subjected to a HPLC analysis...

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The crystal structure of lidocaine hydrochloride monohydrate

Cited by 31 publications

References 2 publications

Optimal Requirements for High Affinity and Use-Dependent Block of Skeletal Muscle Sodium Channel by N-Benzyl Analogs of Tocainide-Like Compounds

Optimal Requirements for High Affinity and Use-Dependent Block of Skeletal Muscle Sodium Channel by N-Benzyl Analogs of Tocainide-Like Compounds

Molecular Origin of Enhanced Proton Conductivity in Anhydrous Ionic Systems

Molecular Complex Consisting of Two Typical External Medicines: Intermolecular Interaction between Indomethacin and Lidocaine

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