Anaesthetic activity

Note that the relative spatial arrangement of the phenyl, amine, and hydroxyl functionahties are identical for (R)-alprenolol and (5)-sotalol. In addition to P-blocking activities, some of these compounds also possess potent local anaesthetic activity (see Anesthetics). The membrane stabilizing activity, however, is not stereoselective and correlates directly with the partition coefficient (hydrophobicity) of the compound. 

Quaternary ammonium salts such as carcainium chloride (RSD 931) have been shown to be antitussive whilst having much reduced local anaesthetic activity. Whilst the molecular mechanisms underlying this antitussive activity is not understood, RSD 931 appears to be A8 fibre selective and may represent a novel class of antitussive drug. More recently JMF2-1 a lidocaine derivative that blocks Na+ channels has had beneficial effects in the airways without significant local anaesthetic activity. 

It is nonselective agent with no local anaesthetic activity and having excellent ocular hypotensive effect preferred for ophthalmic use. It is useful in chronic wide-angle and aphakic glaucoma. Levobunolol and betaxolol are other agents used as ophthalmic preparation used in glaucoma. 

Xenon is an odourless, colourless, non-explosive gas present in the atmospheres of both Earth and Mars in concentrations of approximately 0.08 ppm. Its density is approximately three times and its viscosity twice that of nitrous oxide. Like other noble gases, such as helium and argon, its outer electron shell contains the maximum number of electrons (8) making the molecule highly stable chemically. Despite this, its anaesthetic activity indicates that xenon binds to cell proteins and cell membrane constituents. 

Epidural and intrathecal opioids are widely used for postoperative and obstetric analgesia. In contrast to local anaesthetics, spinal opioids cause minimal sympathetic efferent and motor blockade. Pethidine, which has local anaesthetic activity, can produce sensory and motor blockade. Because remifentanil is formulated with glycine as a vehicle, it should not be used epidurally or intrathecally, since glycine is neurotoxic. 

F Gregan, J Durinda, E Racanska, J Zamocka. Synthesis and local anaesthetic activities of 3-(2-alkoxyphenylcarbamoyloxy)chinuclidinium chlorides. Pharmazie 48 465-466, 1993. 

A series of dibenzazonines with the general structure 111 (R, R, = H, alkyl, alkoxy, halo R2 = H, alkyl R3 = H, alkyl, alkanoyl n = 1,2) were prepared from thebaine (45) and found to have antiarrhythmic activity similar to that of procainamide and local anaesthetic activity lasting longer than that of tetracaine (45). One compound of this series, named asocainol (111, R = R, = H, R2 = Me, R3 = H, n = 2), is a useful drug whose mechanism of action in isolated guinea pig papillary muscles has been studied in detail (78, 79). 

Chelardini, C., Caleotti, N., Di Cesare Mannelli, L., Mazzanti, C. and Bartolini, A. (2001) Local anaesthetic activity of /3-caryophyllene 11. Farmaco 56, 387-389. 

Luduena FP, Hoppe JO (1952) Local anaesthetic activity, toxicity and irritancy of 2-alkoxy analogs of procaine and tetracaine. J Pharm Exp Ther 104 40-53 Luduena FP, Hoppe JO, Coulston F, Drobeck HP (1960) The pharmacology and toxicology of mepivacaine, a new local anesthetic. Toxicol Appl Pharmacol 2 295-315 Luduena FP, Bogado EF, Tullar BF (1972) Optical isomers of mepivacaine and bupivacaine. Arch Int Pharmacodyn 200 359-369... 

Luduena FP, Hoppe JO (1952) Local anaesthetic activity, toxicity and irritancy of 2-alkoxy analogs of procaine and tetracaine. J Pharm Exp Ther 104 40-53... 

When it comes to physicochemical (biological) properties the common structural formulae obscure rather than explain the problem. One of the most convincing examples may be the anaesthetic activity of chemicals. Among general anaesthetics one can identify such diverse chemical families like hydrocarbons, alcohols, ethers, barbiturates, nitrous oxide, steroids, etc. Each one must have anaesthetic activity encoded in its structure but how is it discovered using conventional chemical symbolic The planar or three-dimensional chemical notation can be an obstacle to making a breakthrough in chemistry. 

H. Biich, J. Knabe, W. Buzeilo, and W. Rummel, StereospeciRcity of anaesthetic activity, distribution, inactivation and protein binding of the optical antipodes of two W-methylated barbiturates, /. Pharmacol. Exp. Then, 175 709 (1970). 

Semisynthetic amides of retronamine (66), itself prepared from retronecine (65) in three steps, have been synthesized by coupling with the appropriate acid using AW -dicyclohexylcarbodi-imide. Several of the compounds prepared, notably the p hydroxy benzoyl-, cinnamoyl-, and benzoyl-retronamines, had marked hypotensive activity. The amides could not be crystallized and details of their characterization were not given. Atal and his co-workers have also prepared - a number of semisynthetic diesters of retronecine, heliotridine, and platynedne by esterification of the necine base with the appropriate acid chloride. Several of the compounds prepared had marked local anaesthetic activity. 

A monograph concerned with the configurations and conformations of corticosteroids provides detailed information particularly on mass spectra and and n.m.r., and discusses side-chain conformations of corticosteroids both with and without C-18 oxygen functions the relationships between biological activity and conformation are discussed. The structural features and conformations compatible with anaesthetic activity in pregnane derivatives have also been reviewed. ... 

SMOOTH MUSCLE RELAXANT and ANTISPASMODIC with SOme LOCAL ANAESTHETIC activity. 

According to the equation, anaesthetic activity increases with increasing hydrophobicity (P), as determined by the logP factor. The negative (logP)2 factor shows that the relationship is parabolic and that there is an optimum value for log P (log P°) beyond which increasing hydrophobicity causes a decrease in anaesthetic activity. 

With this equation, it is now possible to predict the anaesthetic activity of other ether structures, given their partition coefficients. 

Since different anaesthetics have similar logP0 values, the logP value of any compound can give some idea of its potential potency as an anaesthetic. For example, the log P values of the gaseous anaesthetics ether, chloroform, and halothane are 0.98, 1.97, and 2.3 respectively. Their anaesthetic activity increases in the same order. 

Roy, K., Pal, D.K, De, A.U. and Sengupta, C. (2001) Comparative QSAR studies with molecular negentropy, molecular connectivity, STIMS and TAU indices. Part 11. General anaesthetic activity of... 

Jussofie, A. (1993) Brain area specific differences in the effects of neuroactive steroids on the GABA Receptor complexes following acute treatment with anaesthetically active steroids. Acta Endocrinology, 129, 480 85. 

Escribano, E., Obach, M., Arevalo, M.I., Calpena, A.C., Domenech, J. and Queralt, J. (2005) Rapid human skin permeation and topical anaesthetic activity of a new amethocaine microemulsion. Skin Pharmacol. Physiol., 18, 294-300. 

Once inside the neuron dissociation is necessary, because it is the ionized form binds to the sodium ion channel. Local anaesthetic activity is dependent on pH, because pH determines the degree of dissociation into ions. This becomes of clinical importance in inflamed and infected tissue, which often has a more acid pH. Acid conditions result in increased degree of ionization and reduced diffusion of local anaesthetic into neurons. This makes them less effective anaesthetics. 

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