Nicotine peripheral pharmacological

Peripheral Pharmacological Actions of Nicotine. Nicotine effects on the cardiovascular system include tachycardia and peripheral vasoconstriction, which leads to elevated blood pressure. Because the cardiovascular effects are mainly caused by elevated levels of catecholamines and cortisol, tolerance to these effects does not occur. Other pharmacological actions of nicotine include increased gastrointestinal motility caused by parasympathetic ganglionic stimulation and skeletal muscle contraction caused by the effect on nicotinic receptors in the neuromuscular junction (184). 

The debut of the selective AChR agonist (+)-anatoxin-a has provided a new tool for AChR physiology and pharmacology. (+)-Anatoxin not only has high affinity for the nicotinic AChR but it also has high selectivity for nicotinic over muscarinic receptors in the mammalian CNS. Recently, the use of (+)-anatoxin-a was essential to the identification of nicotinic receptors on cultured neurons (4), We are studying the features which allow it to bind with high affinity to the peripheral and central nicotinic receptors and the kinetic effects on receptor conformational... 

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

The nAChRs are defined by the alkaloid nicotine and possess a diverse pharmacological profile. This is due to the fact that they are located peripherally at the neuromuscular junctions, ganglia, and parasympathetic fibers where they are composed of four subunits (a ... 

Lockett (36, 37) has described two compounds, base A and base B. Base A occurred in the urine of men (who smoked), women (who did not smoke), and bitches. There was approximately three times as much in the urine of men and bitches as of women. The base was somewhat more active pharmacologically than Z-nicotine, and was found to exert its pressor effect through the mediation of the corpus striatum and thalamus, stimulating the sympathetic nervous system (38). Base A could be converted to -nicotine by drying in a high vacuum, with alteration of its action from a central to a peripheral one therefore it must be very similar in structure to nicotine. Base B was a different compound, also with pressor activity both were obtained by steam distillation from strongly alkaline urine. Furthermore, another compound, which she called base x, appeared in the... 

Swanson, K.L., Aronstam, R.S., Wotmacott, S., Rapoport, H., and Albuquerque, E.X. 1991. Nicotinic pharmacology of anatoxin analogues. 1. side-chain structure-activity-relationships at peripheral agonist and noncompetitive antagonist sites. 

Acetylcholine mediates two different types of activity via corresponding receptors - muscarinic and nicotinic - which relate to the pharmacological activities of two natural prodncts, mnscarine and nicotine. The former type of action occurs in nerve synapses and the latter at nenromnscnlar jnnctions and peripheral ganglia. The term cholinergic is nsed for the general effects of acetylcholine. 

The monoterpenoid-derived alkaloid reserpine (XLV, Fig. 3), the history and pharmacology of which have been the subjects of numerous reviews [251 to 254, 958-969], can be regarded as a structurally specific agent, both on account of the specific nature of its sedative action and because the bewildering complexity of its overall effects probably [969] resides simply in its ability to procure the release of monoamines from their storage sites, both central and peripheral - just as the complex actions of nicotine stem primarily from its action on the ganglia. The structurally specific nature of reserpine would also be borne... 

Other channel and receptor systems in neuronal tissues have been proposed to play a role in the generation of compound-specific clinical symptoms in mammals. The complex nature of the effects of pyrethroids on the central nervous system (CNS) has led various workers to suggest that they also act via modulation of nicotinic cholinergic transmission, reduce peripheral presynaptic adrenoceptor sensitivity [23] which leads to an enhancement of noradrenaline release [24], and affect the serotonin neurotransmission [25]. However, because neurotransmitter-specific pharmacological agents offer only poor or partial protection against poisoning, it is unlikely that any one of these effects represents an alternative primary mechanism of action of the pyrethroids. 

In some species, pharmacological effects other than muscle-relaxation may dominate. Thus, as already seen, the activity of S. erichsonii extracts appears to be due primarily to the presence of diaboline derivatives. Leaf extracts have analgesic properties, while stem-bark extracts have spasmolytic properties and augment the activity of the central nervous system (50). The bark alkaloids of S. glabra are reported to have central rather than peripheral effects (Table 1.4, footnote j). Sublethal doses of aqueous extracts from S. castelnaeana cause hypertension, tachycardia, and slight respiratory stimulation enhancement of the hypertension by atropine and its reduction by hexamethonium (mecamylamine) show that the extract has nicotinic activity. Evidently, the toxicity of the plant must be partly due to the tertiary bases it contains (314). 

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