Procaine derivatives

Single-substituent polymers, such as the procaine derivative shown as compound 24, are insoluble in water. In principle, the bioerosion characteristics can be modified by the presence of amino acid ester, glyceryl, or glucosyl (see later) cosubstituents, and this offers the possibility of a long-term release of a local anesthetic at a targeted site in the body. 

Shen et al. have reported studies on procaine-selective electrodes embodying PVC membranes [57]. Various ion-pair complexes (procaine derivatives with tetraphenylborate, dipicrylamine, tetraiodomecurate, and reineckate) were incorporated into platinized PVC membranes, and with dinonyl phthalate as the solvent mediator, formed procaine selective electrodes. The efficiency and performance of these were compared, and it was found that procaine picrylamine and procaine tetraphenylborate were the best electroactive materials. The procaine picrylamine electrode exhibited a Nemstian response over the range 10 pM to 0.1 M, and was used as the indicator electrode for the potentiometric determination of procaine. The method recovery was found to be 99.8%, with a standard deviation of 0.9%. 

Metoclopramide is structurally related to orthoclopramide, a procaine derivative, and it can prolong the action of suxamethonium because of competition for cholinesterase. However, its common side effects are similar to those seen with phenothiazine derivatives. In high doses, a range of extrapyramidal symptoms may develop. The anti-emetic effects of metoclopramide are due to two main actions. Centrally, it blocks dopamine in the CTZ and peripherally, it hastens gastric emptying, abolishes irregular intestinal contractions, and increases... 

A related approach is to synthesize a polyphosphazene with an amino-drug linked directly to phosphorus through a side-group phosphorus-nitrogen bond. The procaine derivative shown in 3.91 is a typical example designed to release the local anesthetic as an adjunct to dental or minor surgical procedures. Derivatives that contain benzocaine,... 

Procaine derivatives Confusion, doom anxiety, psychosis, agitation, bizarre behavior, depression, panic... 

See Procaine derivatives Mania or hypomania Delirium, hallucinations, paranoia, mania See Benzodiazepines See Thiazides See Atropine and Anticholinergics Psychosis, depression, disorientation, hallucinations, delusions... 

Total penicillins may also be determined by the penicillinase method. For this method buffering substances should not be present as these reduce the sensitivity of the assay and the amount of penicillin being determined should be at least 10 mg. The method is particularly suitable for the assay of salts of penicillin and can be used for the procaine derivative. ... 

Relative to procaine. Data are derived from isolated frog sciatic nerve. 

Among other uses, these polymers have been employed in a variety of biomedical applications. Poly(phosphazenes) containing organic side chains, derived from the anaesthetics procaine and benzocaine, have been used to prolong the anaesthetic effect of their precursor drugs. They have also been used as the bioerodable matrix for the controlled delivery of drugs. 

In this chapter, the voltammetric study of local anesthetics (procaine and related compounds) [14—16], antihistamines (doxylamine and related compounds) [17,22], and uncouplers (2,4-dinitrophenol and related compounds) [18] at nitrobenzene (NB]Uwater (W) and 1,2-dichloroethane (DCE)-water (W) interfaces is discussed. Potential step voltammetry (chronoamperometry) or normal pulse voltammetry (NPV) and potential sweep voltammetry or cyclic voltammetry (CV) have been employed. Theoretical equations of the half-wave potential vs. pH diagram are derived and applied to interpret the midpoint potential or half-wave potential vs. pH plots to evaluate physicochemical properties, including the partition coefficients and dissociation constants of the drugs. Voltammetric study of the kinetics of protonation of base (procaine) in aqueous solution is also discussed. Finally, application to structure-activity relationship and mode of action study will be discussed briefly. 

DIRECT SYNTHESIS FROM N-SILYL-PHOSPHORAMINES CARBORANYL DERIVATIVES BIOACTIVE AND BIOERODABLE POLYMERS (STEROIDS, DOPAMINE, PROCAINE, ETC.)... 

Procainamide (Pwnestyl, Procan SR) is a derivative of the local anesthetic agent procaine. Procainamide has a longer half-life, does not cause CNS toxicity at therapeutic plasma concentrations, and is effective orally. Procainamide is a particularly useful antiarrhythmic drug, effective in the treatment of supraventricular, ventricular, and digitalis-induced arrhythmias. 

Procaine is a derivative of p-aminobenzoic acid, and is a one of the oldest used ester-type local anaesthetic agents [1], The compound was originally developed by Einhom [2,3], and later with and Uhlfelder [4]. This anti-arrhythmic drug itself has a short half-life, but is able to form salts with other drugs which causes an increase in the duration of action [5]. 

A review of the methods which facilitates the rapid choice of an optimum procedure to be used for the determination of procaine and other medicinals derived from aminocarboxylic acids has have been published [28]. This review covers volumetric, optical, electrochemical and polarographic methods. 

Krishna et al. reported a nitritometric method, using aminoanthraquinone dyes as indicators, for the determination of procaine, other 4-amino-benzenesulfonamides, and 4-aminobenzoic acid derivatives [77]. Using sodium dioctyl sulfosuccinate, Faicao and Vianna determined procaine hydrochloride [78]. 

Many substances of widely different chemical structure abolish the excitability of nerve fibers on local application in concentrations that do not cause permanent injury and that may not affect other tissues. Sensory nerve fibers are most susceptible, so that these agents produce a selective sensory paralysis, which is utilized especially to suppress the pain of surgical operation. This property was first discovered in cocaine, but because of its toxicity and addiction liability, it has been largely displaced by synthetic chemicals. The oldest of these, procaine (novocaine), is still the most widely used. Its relatively low toxicity renders it especially useful for injections, but it is not readily absorbed from intact mucous membranes and is therefore not very effective for them. Many of its chemical derivatives are also used. They differ in penetration, toxicity, irritation, and local injury as well as in duration of action and potency. Absolute potency is not so important for practical use as is its balance with the other qualities. If cocaine is absorbed in sufficient quantity, it produces complex systemic actions, involving stimulation and paralysis of various parts of the CNS. These are mainly of toxicological and scientific interest. Its continued use leads to the formation of a habit, resembling morphinism. This is not the case with the other local anesthetics. 

Administration of papaverine along with trichloroisobutyl alcohol and acetylbromodiethylacetylurea increases the effect of the latter two substances (333). In mice, small doses of papaverine reduce the convulsive effect of procaine not however the lethal dose (334). Papaverine inhibits contractions of excised muscles induced by adenosine derivatives (335). j8-Phenylisopropylamine in relatively high concentration increases the tonus of the vascular musculature of the surviving isolated rabbit aorta. This effect was inhibited by papaverine (336). The effect of papaverine on respiration, blood pressure in dogs and cats, on isolated vessels, on the intestine in situ and in vitro as well as its toxicity in rats was not affected by Nalorphine (337). Premedication... 

Because of cocaine s toxicity and addictive properties, a search began for synthetic substitutes for cocaine. In 1905, procaine was synthesized and became the prototypic local anesthetic for half a century. Newer derivatives include mepivacaine and tetracaine (Figure 13.1). Briefly, the SAR of local anesthetics revolves around their hydrophobicity. Association of the drug at hydrophobic sites, such as the sodium channel, is believed to prevent the generation and conductance of a nerve impulse by interfering with sodium permeability (i.e., elevating the threshold for electrical excitability). 

However signs do change with the "handedness" of the natural isomer so a higher level of distinction is achieved using CD or polarimetric detection. An enormous advantage is derived from the fact that achiral excipients, such as lidocaine, procaine, and benzocaine, often deliberately added to illicit drug preparations to complicate the chromatographic identifications of amphetamine and methamphetamine, present no interference problem whatsoever to CD detection. ORD detection was developed for the analysis of mixtures of pseudoephedrine and ephedrine [47], which because of the connection between anomalous ORD and CD, should be applicable to CD detection in the UV. 

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. 

Actions This Class IA drug, a derivative of the local anesthetic procaine (see p. 117), shows actions similar to those of quinidine. 

It has long been known that intramuscular procaine penicillin can cause some peculiar psychological adverse reactions, and that other penicillin derivatives, such as amoxicillin, can cause psychiatric reactions, such as hallucinations (SEDA-21, 259). In a report from the Netherlands, neuropsychiatric symptoms occurred in six patients who received cefepime for febrile neutropenia (147). The patients, two men and four women, aged 32-75 years, received 6 g/day (n = 5) or 3 g/day (n = 1). 

Hypersensitivity to local anesthetics appears to be related to both chemical structure and the method of administration. Allergic reactions occur most frequently with csler-ba.sed local anesthetic agents (benzoic acid derivatives). Adverse effects include allergic dermatitis, asthmatic attack, or. in extreme cases, death due to anaphylactic shock. Individuals suffering a hypersensitive reaction from one local anesthetic agent are often sensitive to compounds with a. similar structure. For example, patients semsilive to procaine arc often also sensitive to amethocaine... 

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