Local anesthetics, alkaloids

Yohimbine (104), also from the bark of C.johimbe K Schum. and from the roots of R. serpentina (1. ) Benth. has a folk history (unsubstantiated) of use as an aphrodisiac. Its use has been confirmed experimentally as a local anesthetic, with occasional employment for rehef ia angiaa pectoris and arteriosclerosis, but is frequently contraindicated by its undesired renal effects. Yohimbine and some of its derivatives have been reported as hahuciaogenic (70). In addition, its pattern of pharmacological activities ia a variety of animal models is so broad that its general use is avoided. All ten carbon atoms of secologanin (102) as well as the entire skeleton of tryptamine (98, R = H) are clearly seen as iatact portions of this alkaloid. 

O-acyl derivatives thereof have shown potent vasodilatory activity [8]. A number of other hetisine alkaloids have shown diverse biological activities. These include nominine [9] (1) (local anesthetic, anti-inflammatory, and antiarrhythmic), hetisine [9a] (4) (hypotensive), ignavine [10] (5) (analgesic, anti-inflammatory, antipyretic, sedative, antidiuretic), zeravshanisine [9a] (8) (antiarrhythmic and local anesthetic), and tadzhaconine [9a, 11], (9) (antiarrhythmic) (Chart 1.3). 

Once the cocaine has been legally produced from the coca leaf, it is exported to various countries for medicinal use, basically as a topical local anesthetic (applied to the surface, not injected, only treating a particular area). In the United States the crystalline powder is imported to pharmaceutical companies who process and package the cocaine for medical use. Merck Pharmaceutical Company and Mallinckrodt Chemical Works distribute cocaine in crystalline form (Hydrochloride Salt) in dark colored glass bottles to pharmacies and hospitals throughout the United States. Cocaine, in the alkaloid form (base drug containing no additives such as hydrochloride in the crystalline form) is rarely used for medicinal purposes. Cocaine hydrochloride crystals or flakes come in Vs, A and 1 ounce bottles from the manufacturer and has a wholesale price of approximately 20 to 25 per ounce (100% pure). 

Puffer fish Fugu spp. Tetrodotoxin (found in Vibrio, Pseudomonas spp.) Alkaloid Predators. Local anesthetic (5-30 minutes) death in 6-24 hours (60% mortality)... 

California newt Tetrodotoxin Alkaloid Local anesthetic. 

Belladonna alkaloids have an extremely broad pharmacological spectrum. In addition to their ability to block M-receptors, atropine and scopolamine also act on other receptors, thus showing corresponding effects. They can only block nicotinic cholinergic receptors, however, in significantly larger doses than those used in clinics. Atropine also exhibits properties of local anesthetics and histamine (Hj) receptor blockers. Atropine and... 

Cocaine (4.73), the local anesthetic tropane alkaloid of coca leaves, is a potent NE reuptake inhibitor but has no antidepressant activity. 

Cocaine is an alkaloid found in the leaves of Erythroxylon coca, a shrub indigenous to the Andes. For more than 100 years, it has been extracted and used in clinical medicine, mainly as a local anesthetic and to dilate pupils in ophthalmology. Sigmund Freud famously proposed its use to treat depression and alcohol dependence, but addiction quickly brought an end to this idea. 

The natural alkaloid cocaine was introduced as the first local anesthetic drug in clinical surgery... 

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

With the exception of local application of ethylmorphine to the conjunctiva or the tympanum to produce hyperemia, there are no rational local uses of opium alkaloids. These drugs are not local anesthetics and relieve pain only by central actions. Indeed, irritation and vesication may result from opium plasters, ointment, or washes applied to the skin or mucosa. 

Toxicants may have three effects on pulse rate bradycardia (decreased rate), tachycardia (increased rate), and arrhythmia (irregular pulse). Alcohols may cause either bradycardia or tachycardia. Amphetamines, belladonna alkaloids, cocaine, and tricyclic antidepressants (see imi-primine hydrochloride in Figure 6.12) may cause either tachycardia or arrhythmia. Toxic doses of digitalis may result in bradycardia or arrhythmia. The pulse rate is decreased by toxic exposure to carbamates, organophosphates, local anesthetics, barbiturates, clonidine, muscaric mushroom toxins, and opiates. In addition to the substances mentioned above, those that cause arrhythmia are arsenic, caffeine, belladonna alkaloids, phenothizine, theophylline, and some kinds of solvents. 

Little of value has come out of pharmacological studies on these alkaloids (34) local anesthetic properties (35) have been reported, and none of the alkaloids have shown antimalarial properties (36). 

There have been no recent studies on the pharmacology of samandarine alkaloids. Samandarine is a potent local anesthetic 48). Cardiac depressant effects (48,49) and inhibition of binding of a radiolabeled batracho-toxin analog to sodium channels (50) are consonant with the potent local anesthetic activity of samandarine. Samandarine alkaloids show antimicrobial activity (51 and references therein). 

Procaine hydrochloride was first synthesized by Einhorn in 1905 as a substitute for cocaine, the first local anesthetic. Cocaine, an alkaloid obtained from the leaves of the coca plant, Erythroxylon coca, is highly addictive and toxic. Procaine hydrochloride replaced cocaine as a local anesthetic because it is much less toxic, cheaper and easier to produce, and it is easier to sterilize. In contrast to cocaine, it is not addictive because it is less stimulating to the central nervous system. 

Coca-Cola was originally flavored with extracts from the leaves of the coca plant and the kola nut. Coca is grown in northern South America the Indians of Peru and Bolivia have for centuries chewed the leaves to relieve the pangs of hunger and high mountain cold. The cocaine from the leaves causes local anesthesia of the stomach. It has limited use as a local anesthetic for surgery on the eye, nose, and throat. Unfortunately it is now a widely abused illicit drug. Kola nuts contciin about 3% caffeine as well as a number of other alkaloids. The kola tree is in the same family as the cacao tree from which cocoa cmd chocolate cu-e obtained. Modem cola drinks do not contain cocaine however, Coca-Cola contains 43 mg of caffeine per... 

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