Noradrenergic mechanisms, drugs

Effects of narcotic analgesic drugs on brain noradrenergic mechanisms Smith, Charles Bruce Sheldon, M. I. 

Experimental studies have shown that the release of a transmitter from a nerve terminal can be decreased or increased by a variety of other neurotransmitters. For example, stimulation of 5-HT receptors on noradrenergic terminals can lead to an enhanced release of noradrenaline. While the physiological importance of such a mechanism is unclear, this could be a means whereby drugs could produce some of their effects. Such receptors have been termed heteroceptors (Figure 2.3). 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

Pharmacologic targeting of monoamine transporters. Commonly used drugs such as antidepressants, amphetamines, and cocaine target monoamine (norepinephrine, dopamine and serotonin) transporters with different potencies. A shows the mechanism of reuptake of norepinephrine (NE) back into the noradrenergic neuron via the norepinephrine transporter (NET), where a proportion is sequestered in presynaptic vesicles through the vesicular monoamine transporter (VMAT). and C show the effects of amphetamine and cocaine on these pathways. See text for details. 

Svensson TH, Usdin T (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants a-receptor mediation. Science 202 1089-91 Svensson TH, Bunney BS, Aghajanian G (1975) Inhibition of both noradrenergic and serotonergic neurons in the brain by the a-adrenergic agonist clonidine. Brain Res 92 291-306 Szabo B (2002) Imidazoline antihypertensive drugs a critical review on their mechanism of action. Pharmacol Therapeut, 93 1-35... 

Bupropion s effectiveness as a smoking cessation agent is not related to its antidepressant effect. The drug is equally effective in smokers with current depression, past depression, or no depression (168). The mechanism by which bupropion enhances the ability for smoking cessation is believed to be related to its dopaminergic and noradrenergic activity... 

The mechanism of action of cyclobenzaprine is thought to result from an increase in stimulation of central a2 receptors and subsequent decrease in noradrenergic activity. New evidence, however, suggests that the antagonist actions of the drug at 5-HT, receptors are responsible for the muscle relaxation effect. 

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