Anxiety monoamines

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

The term pasaon flower is used to denote many of the approximately 400 species of the herb. F saon flower has been used in medicine to treat pain, anxiety, and insomnia. Some herbalists use the herb to treat symptoms of parkinsonism. F saon flower is often used in combination with other herbs , such a valerian, chamomile, and hops, for promoting relaxation, rest and sleep. Although no adverse reactions have been reported, large doses may cause CNS depression. The use of passion flower is contraindicated in pregnancy and in patientstaking the monoamine oxidase inhibitors (MAOIs). Fission flower contains coumarin, and the risk of bleeding may be increased when used in patientstaking warfarin and pasaon flower. 

The evidence outlined so far does little to explain how monoamines or anti-anxiety drugs might influence anxiety states. To achieve this, an integrated view of the relevant brain systems is required, together with an appreciation of how their function is regulated. 

Finally, as outlined above, descending monoamine systems, originating in the midbrain and brainstem that act through the spinal release of noradrenaline and 5-HT, modulate the spinal transmission of pain. Alphai adrenoceptors appear to be important in this role but it is unlikely that behavioural effects such as sedation can be separated from the analgesia. Since both noradrenaline and 5-HT are key transmitters in the control of mood and anxiety and yet also participate in the control of sensory events that lead to... 

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Blockers are contraindicated in patients with decompensated heart failure unless it is caused solely by tachycardia (high output). Other contraindications include sinus bradycardia, concomitant therapy with monoamine oxidase inhibitors or tricyclic antidepressants, and patients with spontaneous hypoglycemia. Side effects include nausea, vomiting, anxiety, insomnia, lightheadedness, bradycardia, and hematologic disturbances. 

Monoamine Oxidase inhibitors (MAOis). Many, though not all, antidepressants are effective treatments for social anxiety disorder. Although they do not provide rapid symptom relief and may even transiently worsen anxiety symptoms during the first 1-2 weeks of treatment, antidepressants have the advantage of treating comorbid depression. 

Monoamine Oxidase Inhibitors (MAOIs). As mentioned earlier, the MAOIs are excellent treatments for both depression and anxiety. They act by increasing neurotransmission of three neurotransmitter systems serotonin, norepinephrine. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Patients with marked anxiety, tension, and agitation, because the drug may aggravate these symptoms hypersensitivity to methylphenidate or other components of the product patients with glaucoma, motor tics, or a family history or diagnosis of Tourette s syndrome during treatment with monoamine oxidase inhibitors (MAOIs), and also within a minimum of 14 days following discontinuation of an MAOl (hypertensive crises may result). 

Examples of monoamine oxidase inhibitors are phenelzine, tranylcypromine, isocarboxazid and mo-clobemide. They are indicated for atypical depression. Changes in the neurotransmitter levels are seen in several days but the clinical effect may lag by several weeks. Phenelzine is a non-selective hydrazine-type monoamine oxidase inhibitor while the also non-selective inhibitor tranylcypromine is of the non-hydrazine-type. Phenelzine, tranylcypromine and isocarboxazid are irreversible inhibitors. Phenelzine is partly metabolized by acetylation and slow acetylators are more prone to toxicity. It has anxiolytic properties and superior efficiacy in treating severe anxiety. 

Another major focus of interest for the investigation of anxiety disorders is the monoamine neurotransmitter serotonin (5-HT see also chapter by Mohler et al., this volume) because of reduced levels of 5-HT receptors found in patients... 

AC VIII, adenylyl cyclase type VIII BDNF, brain-derived neurotrophic factor CamKII, calcium-calmodulin kinase II GIRK2, G protein-activated inward rectifying potassium 2 MAOA, monoamine oxidase A n.d., not determined NCAM, neural cell adhesion molecule nNOS, neuronal nitric oxide synthase Petl, ETS domain transcription factor tPA, serine protease tissue-plasminogen activator (tPA). t/ > Increase/decrease in anxiety-related behavior. No effect. 

Brunner D, Buhot MC, Hen R, Hofer M (1999) Anxiety, motor activation, and maternal-infant interactions in 5HT1B knockout mice. Behav Neurosci 113 587-601 Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262 578-580... 

The biology of the monoamines is described in detail elsewhere. In simple terms, they facilitate transmission in neural pathways that originate in nuclei of the brainstem and have descending projections to the autonomic nervous system and widespread ascending projections to sites in the limbic system and cortex. These pathways modulate many aspects of behavioural function as well as anxiety responses. Of the three monoamines, the role of serotonin in anxiety is best understood, but the picture is complex as increased serotonergic activity may be anxiogenic or anxiolytic depending on the site of action (Bell and Nutt 1998). 

The growth during the 1990s in the use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), for the treatment of anxiety disorders represented a major advance in the pharmacotherapy of anxiety. The efficacy of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) had been established alongside their antidepressantw actions several decades... 

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