Saturday, February 14, 2015

Monoamine Oxidase Inhibitors (MAOIs)

Wikipedia:
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). All monoamines are derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan, and the thyroid hormones by the action of aromatic amino acid decarboxylase enzymes.

Monoaminergic systems, i.e., the networks of neurons that utilize monoamine neurotransmitters, are involved in the regulation of cognitive processes such as emotion, arousal, and certain types of memory. It has been found that monoamine neurotransmitters play an important role in the secretion and production of neurotrophin-3 by astrocytes, a chemical which maintains neuron integrity and provides neurons with trophic support. Drugs used to increase the effect of monoamine may be used to treat patients with psychiatric disorders, including depression, anxiety, and schizophrenia.

Specific transporter proteins called monoamine transporters that transport monoamines in or out of a cell exist. These are the dopamine transporter (DAT), serotonin transporter (SERT), and the norepinephrine transporter (NET) in the outer cell membrane and the vesicular monoamine transporter (VMAT1 and VMAT2) in the membrane of intracellular vesicles.

After release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal. There, they can be repackaged into synaptic vesicles or degraded by the enzyme monoamine oxidase (MAO), which is a target of monoamine oxidase inhibitors, a class of antidepressants.

Wikipedia:
Monoamine oxidases catalyze the oxidative deamination of monoamines. They are well known enzymes in pharmacology, since they are the substrate for the action of a number of monoamine oxidase inhibitor drugs. MAO-A is particularly important in the catabolism of monoamines ingested in food. Both MAOs are also vital to the inactivation of monoaminergic neurotransmitters, for which they display different specificities.
  • Serotonin, melatonin, noradrenaline, and adrenaline are mainly broken down by MAO-A.
  • Phenethylamine and benzylamine are mainly broken down by MAO-B.
  • Both forms break down dopamine, tyramine, and tryptamine equally.

Wikipedia:
Monoamine oxidase inhibitors (MAOIs) act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine. MAO-B preferentially deaminates phenethylamine and trace amines. Dopamine is equally deaminated by both types.

They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson's Disease and several other disorders. MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar depression according to a recent retrospective-analysis.

Because of potentially lethal dietary and drug interactions, MAOIs have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed. MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRIs, tricyclics, MDMA, meperidine, tramadol, and dextromethorphan. Agents with actions on epinephrine, norepinephrine, or dopamine must be administered at much lower doses due to potentiation and prolonged effect.

Nicotine, a substance frequently implicated in tobacco addiction, has been shown to have "relatively weak" addictive properties when administered alone. The addictive potential increases dramatically after co-administration of an MAOI, which specifically causes sensitization of the locomotor response in rats, a measure of addictive potential. This may be reflected in the difficulty of smoking cessation, as tobacco contains naturally-occurring MAOI compounds in addition to the nicotine.

Wikipedia:
Banisteriopsis caapi, also known as ayahuasca, caapi or yajé, is a South American jungle vine of the family Malpighiaceae. It is used to prepare ayahuasca, a decoction with a long history of entheogenic uses as a medicine and "plant teacher" among the indigenous peoples of the Amazon Rainforest. It contains harmine, harmaline, and tetrahydroharmine, all of which are both beta-carboline harmala alkaloids and MAOIs. The MAOIs in B. caapi allow the primary psychoactive compound, DMT (which is introduced from the other primary ingredient in ayahausca, the Psychotria viridis plant), to be orally active. The stems contain 0.11-0.83% beta-carbolines, with harmine and tetrahydroharmine as the major components. Alkaloids are present in all parts of the plant.

The name ayahuasca means "vine of the soul" in Quechuan, and the shamans of the indigenous western Amazonian tribes use the plant in religious and healing ceremonies. In addition to its hypnotic effect, caapi is used for its healing properties as a purgative, effectively cleansing the body of parasites and helping the digestive tract. Vomiting can follow ayahuasca ingestion; this purging is considered by many shamans and experienced users of ayahuasca to be an essential part of the experience, as it represents the release of negative energy and emotions built up over the course of one's life.

People who have consumed ayahuasca report having spiritual revelations regarding their purpose on Earth, the true nature of the universe as well as deep insight into how to be the best person they possibly can. This is viewed by many as a spiritual awakening and what is often described as a rebirth. In addition, it is often reported that individuals feel they gain access to higher spiritual dimensions and make contact with various spiritual or extra-dimensional beings who can act as guides or healers.

The ingestion of ayahuasca can also cause significant, but temporary, emotional and psychological distress (the "bad trip" experience). Long-term negative effects are not known. However, deaths due to participation in the consumption of ayahuasca have been reported.

University of Bristol:
2-phenylethylamine (PEA) is a trace amine, found in very small amounts in the human body. It is the parent of the amphetamines, such as methamphetamine. Brain concentrations of 2-phenylethylamine are significantly increased by monoamine oxidase inhibitor antidepressants; urinary concentrations of phenylacetic acid are increased following exercise, suggesting that phenylethylamine may be involved in the "runner's high", the state of euphoria associated with a level of physical exercise.

More information:
» Molecule of the Month: Methamphetamine (and its Isomers)

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