Posted by Shawn. T. on January 4, 2004, at 23:21:05
In reply to Norepenephrine: What Is Its Function?, posted by SandyWeb on January 4, 2004, at 12:06:19
Among other actions, mirtazapine blocks the activity of norepinephrine at alpha-2 norepinephrine receptors. Some of these receptors (autoreceptors) are involved in controlling the release of norepinephrine from cell bodies in the locus coeruleus region of the brain. At higher doses, mirtazapine can increase the release of norepinephrine by blocking the effect of inhibitory alpha-2 autoreceptors. This effect would probably be most evident at doses above 30 mg/day. The med most similar in function is mianserin, which is not sold in the U.S. Other alpha-2 antagonists include yohimbine and idazoxan.
Norepinephrine is the primary neurotransmitter of the sympathetic nervous system. I'm sure that you're more interested in its functions in the brain; here are a few good descriptions:
Norepinephrine by Gary Aston-Jones (in Neuropsychopharmacology: The Fifth Generation of Progress): http://www.acnp.org/g5/p/SCH4_47-58.pdf
...
Berridge CW, Waterhouse BD.
The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes.
Brain Res Brain Res Rev. 2003 Apr;42(1):33-84.
Through a widespread efferent projection system, the locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. Initial studies provided critical insight into the basic organization and properties of this system. More recent work identifies a complicated array of behavioral and electrophysiological actions that have in common the facilitation of processing of relevant, or salient, information. This involves two basic levels of action. First, the system contributes to the initiation and maintenance of behavioral and forebrain neuronal activity states appropriate for the collection of sensory information (e.g. waking). Second, within the waking state, this system modulates the collection and processing of salient sensory information through a diversity of concentration-dependent actions within cortical and subcortical sensory, attention, and memory circuits. Norepinephrine-dependent modulation of long-term alterations in synaptic strength, gene transcription and other processes suggest a potentially critical role of this neurotransmitter system in experience-dependent alterations in neural function and behavior. The ability of a given stimulus to increase locus coeruleus discharge activity appears independent of affective valence (appetitive vs. aversive). Combined, these observations suggest that the locus coeruleus-noradrenergic system is a critical component of the neural architecture supporting interaction with, and navigation through, a complex world. These observations further suggest that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective disorders, including post-traumatic stress disorder. Independent of an etiological role in these disorders, the locus coeruleus-noradrenergic system represents an appropriate target for pharmacological treatment of specific attention, memory and/or arousal dysfunction associated with a variety of behavioral/cognitive disorders.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12668290&dopt=Abstract...
Aston-Jones G, Rajkowski J, Cohen J.
Role of locus coeruleus in attention and behavioral flexibility.
Biol Psychiatry 1999 Nov 1;46(9):1309-20
Previous findings have implicated the noradrenergic locus coeruleus (LC) system in functions along the dimension of arousal or attention. It has remained uncertain what role this system has in attention, or what mechanisms may be involved. We review our recent work examining activity of LC neurons in monkeys performing a visual discrimination task that requires focused attention. Results indicate that LC cells exhibit phasic or tonic modes of activity, that closely correspond to good or poor performance on this task, respectively. A computational model was used to simulate these results. This model predicts that alterations in electrotonic coupling among LC cells may produce the different modes of activity and corresponding differences in performance. This model also indicates that the phasic mode of LC activity may promote focused or selective attention, whereas the tonic mode may produce a state of high behavioral flexibility or scanning attentiveness. The implications of these results for clinical disorders such as attention-deficit hyperactivity disorder, stress disorders, and emotional and affective disorders are discussed.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10560036&dopt=Abstract...
You can find more information on the relationship between norepinephrine and depression at http://www.neurotransmitter.net/nedepression.html and more information on mirtazapine at http://www.neurotransmitter.net/mirtazapine.html
Shawn
poster:Shawn. T.
thread:296341
URL: http://www.dr-bob.org/babble/20031231/msgs/296547.html