Local anaesthetic actions

Homatropine (mandelyltropine) being a useful mydriatic it is surprising that of nine esters of mandelic acid tried, none showed mydriatic activity though three were local anaesthetics, two of them being described as good. Only one of the tropic acid esters tried showed local anaesthetic action and that was poor. ... 

Enterprise in the synthesis of new local anaesthetics shows no sign of diminution and several useful reviews dealing with the correlation of structure and local anaesthetic action have been published of which that by Moore deals generally with the subject, while Gilman, Goodman, Thomas, Hahn and Priitting discuss structure and acti-vity in... 

The lupinane group has not attracted chemists as a primary material for modification in the hope of developing substances of possible therapeutic interest. Liberalli found lupanine was inactive in avian malaria and Clemo and Swan state that this is also the case for ll-(e-diethylamino- -pentyl)aminolupinane. Lupinine -aminobenzoate has been investigated in Russia and shown to possess marked local anaesthetic action. ... 

Cotarnine resembles hydrastinine (p. 167) in its pharmacological effects, but Its action on the uterus is less marked. It does not constrict the arterioles and appears to have a depressant action on the heart. Magidson and Gorbovizki have shown 1 that the Schiff s bases formed by the condensation of aldehydes with 1-aminomethylanhydrocotarnine have a marked local anaesthetic action but are irritant. 

A series of papers on the pharmacological action of akuammine has been published by Raymond-Hamet in which it is established inter alia that the alkaloid has a local anaesthetic action almost equal to that of cocaine. 

Temocin. Has nicotine a local anaesthetic action J Basic Clin Physiol Pharmacol 1994 5(2) 125-131. 

Usami, and K. Takamura. Local anaesthetic action of the Chinese medicine saiko-keishi-to. Planta Med 1979 37 ... 

Topical administration It is employed for local action in the form of ointments, creams, jellies etc. for its antiseptic and local anaesthetic action. The lipid soluble drugs penetrate the skin easily and rapidly. 

Local anaesthetic Chlorpromazine has a potent local anaesthetic action. 

The coexistence of lipid and water solubility in the same molecule is essential for the action of a local anaesthetic drug. Lipophilicity permits the migration of drug across the phospholipid membrane of the nerve cell hydrophilicity is essential for the ionisation of the drug within the nerve. It follows that lipid and water solubility are the external and internal facilitators of local anaesthetic action in the nerve cell. Both within and without the nerve cell the unionised and ionised forms coexist in dynamic equilibrium. Outside the nerve, the active species is the unionised tertiary amine form. Conversely, inside the cell the ionised form predominates. The lower intracellular pH induces a shift in the equilibrium in favour of ionisation (Figure 5.5). 

Some local anaesthetics, such as benzocaine, are totally insoluble in water and cannot ionise. Consequently, there is no cation and therefore no Na+ channel block from within the cell. It is suggested that agents, such as benzocaine, which are very lipid-soluble, exert their effect in the phospholipid bilayer of the axon. This is the basis of the membrane expansion theory of local anaesthetic action. It is also possible that they diffuse laterally form the bilayer into the Na+ channel without ever accessing the axoplasm and in effect produce another variety of Na+ channel block. Repetitive depolarisation of a nerve recruits more Na+ channels and maintains them in the open state for a longer period than normal. 

Finally, Weiner and Zilkha (36) have investigated die prolongation of the local anaesthetic action of procain, bound to tetraethylene glykol or polyethylene glykol) 4004 [7]. The tetraethyleneglykol derivative showed an extended and stronger activity. 

Page 49, figure 5.5 Toxicology Letters 100-101 247-254 (1998), French R.J. et al Molecular and kinetic determinants of local anaesthetic action on sodium channels. Reprinted with permission from Elsevier. 

Vasoconstriction will reduce local blood flow so that distribution of drug away from an injection site is retarded, e.g. local anaesthetic action is prolonged by combination with adrenaline (epinephrine). 

A cooling application such as 0.5-2% menthol in aqueous cream is antipruritic, probably by weak local anaesthetic action. 

Local anaesthetic action on peripheral nerves is also proportional to P since the unionised form must diffuse across the continuous cell layer of the perineurium. Once across the perineurium, the molecules ionise and they combine with the receptors in the nerve membrane in their ionised form. 

His academic research was focused to provide training for the 50 Ph.D. students who benefited from his tutelage. Work on the synthesis and reactions of azodicarboxylic esters that had been started at Goodyear was continued, p-dialkylaminoethyi esters of stericaily hindered alkyl-substituted benzoic acids were made that had longer local anaesthetic action than Procaine, and azo-nitrogen analogs of unsaturated acids and their derivatives were studied for potential... 

Horrobin DF, Durand LG, Manku MS. Prostaglandin El modifies nerve conduction and interferes with local anaesthetic action. Prostaglandins 1977 14 103-108. 

For the coca-chewing Indians in South America, on the other hand, the central stimulant effect is the wanted effect, whereas the local anaesthetic action is an undesired side-effect. The dried leaves (which are purchased on the local market, (see Fig. 20) are mixed with alkali (burned bones from llamas, which is called Lliptar) the mixture is kept between the teeth and cheek, without direct chewing, and the saliva is swallowed. Coca chewing gives rise to less dependence and social problems than the use of isolated cocaine in the form of inhaled cocaine hydrochloride or the smoked free-base alkaloid called Crack or Free-base . 

It is mostly employed as a topical anaesthetic for the relief of insect bites, hemmoroids, and minor wounds. As the drug shows a stinging and burning sensation, hence it must not be used for the eyes, nose and throat at all. The local anaesthetic action commences in 3-5 minutes its potency is fairly comparable to that of benzocaine and is not adequate to abolish the gag reflex. It is also indicated in a 1% (w/v) solution for the rapid relief of pain in rectal surgery, episiotomies, anogenital pruritus, itching dermatoses and minor bums. 

The menthol synthesis is all the more remarkable because three chiral centers are created, all of which are necessary to produce the characteristic menthol odour and local anaesthetic action. 

The fact that local anaesthetic action can be partially reversed by high external pressure (Kendig and Cohen, 1977) may point to an additional, non structurally specific, contribution to local anaesthetic action (Metcalfe and Burgen, 1968). This would not be surprising for at least one substance in ten, selected at random, has local anaesthetic action, however slight, usually accompanied by an unfavourable therapeutic index. 

No account of sodium channels in excitable membranes would be complete without some mention of local anaesthetic drugs. Some new aspects of local anaesthetic action are included, particularly since they infringe on the mechanisms of sodium channels in excitable membranes. 

Prisms from ligroin. M.p. 87-8°. Sol, EtOH, EtjO, CHCI3, CgHg. Insol. HjO. Possesses no local anaesthetic action. 

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