Alkaloids cholinergic

Carbamate Insecticides. These are stmcturaUy optimi2ed derivatives of the unique plant alkaloid physostigmine [57-47-6] a cholinergic dmg isolated in 1864 from Phjsostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The A/,A/-dimethylcarbamates of heterocycHc enols (36) and the Ai-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the A/-methylcatbamates of oximes have subsequentiy been found to be effective systemic insecticides. 

A crude alkaloidal fraction from the stem of Tabernaemontana pandacaqui decreased the motor activity, respiratory rate, induced ataxia, antinociception, and loss of screen grip in rats, suggesting a CNS depression. The extract brought about the prolongation of pentobarbital sleeping time and the oxotremorine-induced salivation, hence possible cholinergic effects (13). 

Acetylcholine receptors have been classified into sub-types based on early studies of pharmacologic selectivity. Long before structures were known, two crude alkaloid fractions, containing nicotine and muscarine (Fig. 11-2), were used to subclassify receptors in the cholinergic nervous system (Fig. 11-3). The greatly different... 

Thus, cholinergic receptor classification can be considered in terms of three stages of development. Initially, Dale [2] distinguished nicotinic and muscarinic receptor subtypes with crude alkaloids. Then, chemical synthesis and structure-activity relationships clearly revealed that nicotinic and muscarinic receptors were heterogeneous, but chemical selectivity could not come close to uncovering the true diversity of receptor subtypes. Lastly, analysis of subtypes came from molecular cloning, making possible the classification of receptors on the basis of primary structure (Fig. 11-2). 

The cholinergic hallucinogens all have common chemical constituents that are responsible for their pharmacological effects (Robbers et al. 1996). These are the tropane alkaloids hyoscyamine, scopolamine (or hyoscine), and atropine (figure 9.16). It is scopolamine, and not atropine or hyoscyamine, which primarily produces the central and hallucinogenic effects because it is the only one that passes the blood-brain barrier sufficiently. However, all three have peripheral effects. Datura stramonium contains 0.1-0.65% tropane alkaloids, which is principally... 

Lobeline (3), extracted from Lobelia inflate, interacts with the nicotinic receptor and could also be exploited to influence cholinergic function in AD. Other alkaloids such as sophoramine (4) and cytisine (5), found in members of the Leguminosae, also have nicotinic agonistic properties. ... 

The tropane alkaloids, especially hyoscine (scopolamine) (18), have been used to treat PD since they increase DA activity by antagonizing cholinergic activity at the muscarinic receptors in the striatum. The naturally occurring alkaloids, foimd in various genera of the Solanaceae, are not... 

Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the fact that muscarine does not have any therapeutic value, it is of interest because of its expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine, muscarine does not act on nicotinic receptors. 

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... 

The clinical application of alkaloids involves them as agents to regulate mescaric cholinergic receptor activity and repairing possible disturbances or to correct possible defects. Atropine, hyoscine and hyoscyamine may all have these kinds of applications. 

The muscarinic cholinergic receptor is competitively blocked by hyoscine and hyoscyamine. Both of these alkaloids are more active than atropine. The applications of these alkaloids for clinical purposes are connected with the induction of general anaesthesia. Clinical consideration should be paid to the fact that these alkaloids also affect the brain and thereby the central nervous system. Atropine crosses the blood-brain barrier. Hyoscine and hyoscyamine depress the motor areas of the cerebral cortex. 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

Other cholinergic agonists have no therapeutic use. Muscarine (4.3) is an alkaloid of the mushroom Anumita muscaria muscarone (4.9) is its semisynthetic analog. Pilocarpine (2.2) is found in the leaves of a shrub and can be used to increase salivation or sweating. Arecoline (4.10) is also an alkaloid, and occurs in the betel nut that is used as a mild euphoriant in India and Southeast Asia. Finally, oxotremorine (4.11) is a synthetic experimental agent that produces tremors and is helpful in the study of antiparkinsonian drugs. 

The cholinergic blocking agents which mainly include atropine and related alkaloid are obtained from the plant Atropa belladonna (deadly nightshade), Atropa acuminata, Hyoscyamus niger (black henbane) and Datura stramonium (datura) and semisynthetic atropine/hyoscine analogues and synthetic compounds. 

Acetylcholine (ACh) is an example of an endogenous neurotransmitter that binds to more than one receptor type, the nicotinic acetylcholine receptor (nAChR) which preferentially binds nicotine and the muscarinic receptor which binds muscarine, a mushroom alkaloid. The latter is a G protein-coupled receptor while the nACh receptor is an excitatory ligand-gated ion channel that transports Na-i- ions. Nicotinic cholinergic receptors are found in the CNS, autonomic ganglia, and at the neuromuscular junction of skeletal muscles. They are a possible target for anaesthetics. 

Acetylcholine receptors. There are numerous receptors for ACh (Fig. 12—10), of which the major subtypes are nicotinic and muscarinic subtypes of cholinergic receptors. Classically, muscarinic receptors are simulated by the mushroom alkaloid muscarine and nicotinic receptors by the tobacco alkaloid nicotine. Nictotinic receptors are all ligand-gated, rapid-onset, and excitatory ion channels, which are blocked by curare. Muscarinic receptors, by contrast, are G protein—linked, can be excitatory or inhib-... 

Flupenthixol and procyclidine Fluphenazine Prednisone and salbutamol Betal nut (Areca catechu) Rigidity, bradykinesia, jaw tremor Betal contains arecoline, a cholinergic alkaloid Tremor, stiffness, akithesia Inadequate control of asthma Arecoline challenge causes dose-related bronchoconstriction in patients with asthma... 

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