Central Nervous stem Stimulants

The securinega alkaloids occur in several species of the Securinega and Phyllan-thus genera (150). Securinine was first isolated from the leaves and stems of Securinega suffruticosa (Euphorbiaceae). Securinine nitrate is a central nervous system stimulant similar to strychnine but less toxic. It was found to be useful in treatment of paresis and paralysis following infectious diseases and psychic disorders. The related alkaloids were obtained from Securinega suffruticosa allose-curinine, dihydrosecurinine, securinol A, and securinol B from the leaves, and securitinine from the roots. 

Strychnine is an alkaloid that is fonnd in Nux vomica. It causes excitation of aU parts of the central nervous system, with a characteristic motor pattern. Strychnine is a competitive antagonist at inhibitory neurotransmitter glycine receptors in the spinal cord, brain stem, and higher centers. It thus increases neuronal activity and excitability, leading to increased muscular activity. Since strychnine convulsions also occur in decerebrate animals, the convulsion is termed a spinal convulsion, but other parts of the central nervous system are also stimulated... 

Studies in brain slices have shown that histamine is one of the most powerful agents in stimulating cyclic AMP accumulation in the mammalian central nervous system [ 146]. Early studies in the rabbit showed that histamine elicited very large increases in the accumulation of cyclic AMP in cerebral cortex (12-16-fold increase above basal levels), hypothalamus (20-30-fold), brain stem (35-fold) and cerebellum (3-10-fold) [155, 156]. The effect in cerebral cortex has subsequently been studied by a number of other groups and increases in cyclic AMP accumulation as high as 74-fold above basal levels have been reported [82, 157, 158]. Furthermore, the response to histamine in rabbit cerebral cortical slices appears to depend on the age of the animal and increases markedly during the first 8 days postpartum before declining to adult levels [157],... 

There are four major groups of medications that stimulate the central nervous system. These are amphetamines, caffeine, analeptics, and anorexiants. Amphetamines stimulate the cerebral cortex of the brain. Caffeine also stimulates the cerebral cortex and stimulates respiration by acting on the brain stem and medulla. Analeptics have an effect on the brain stem and medulla as caffeine does. Anorexiants inhibit appetite by stimulating the cerebral cortex and the hypothalamus. 

The use of khat (Catha edulis, Celastraceae) is common in several areas of northeastern Africa and in Yemen. Although the leaves and young stems are usually used as a masticatory, a tea is sometimes prepared (Brenneisen and ElSohly, 1992). The active compounds of khat are two closely related compounds i-pseudonorephedrine (35) and (- )-a-aminopropiophenone or cathinone (36) (Crombie et al., 1990 Szendrei, 1980) (see also Chapter 36). These compounds have central nervous stimulant activity (Tyler et al., 1981). (5)-Cathinone is thought to be responsible for the cardiac stimulating activity of khat (Wagner, 1988). 

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). 

Other recent reports which indirectly tend to weaken the concept that norepinephrine is the sole alerting neurohumor indicate that (1) imipramine hyperactivity may result from blocking uptake and reducing nervous impulse flow in central serotonin neurons (2) drugs which Inhibit uptake of catecholamines also block serotonin accumulation in rabbit brain stem preparations (3) the increase in overt stimulation caused by 5-hydroxy-tryptophan may be associated with Impaired norepinephrine synthesis rather than increased norepinephrine release and (4) norepinephrine and dopamine inhibit electrical activity of central neurons as determined microelectro-phoretically although another study indicated that norepinephrine does cause neuronal excitation ... 

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