Receptor monoamine

Amino acid receptors Monoamine receptors Lipid receptors Purine receptors Neuropeptide receptors Peptide hormone receptors Chemokine receptors Glycoprotein receptors Protease receptors Metabotropic glutamate and GABAb receptors Adrenoceptors, dopamine and 5-HT receptors, muscarinic and histamine receptors Prostaglandin, thromboxane and PAF receptors Adenosine and ATP (P2Y) receptors Neuropeptide Y, opiate, cholecystokinin VIP, etc. Angiotensin, bradykinin, glucagon, calcitonin, parathyroid, etc. Interleukin-8 TSH, LH/FSH, chorionic gonadotropin, etc. Thrombin... 

In the monoamine receptors the ligand-binding domain is located within the transmembrane helices. A pocket is formed between TM3, TM5 and TM6 where the agonist binds. A conserved aspartate residue in TM3 (Asp-113 in the /(-adrenoceptor) and a... 

Ultimately, agonist drugs that directly activate monoamine receptors would appear to be a logical development in this field. Unfortunately, the peripheral side-effects of such compounds could well limit their acceptability even if we were to discover what subset of receptors to target. 

Huang, P., Visiers, I., Weinstein, H., and Fiu-Chen, F.-Y. (2002) The local environment at the cytoplasmic end of TM6 of the m opioid receptor dilfers from those of rhodopsin and monoamine receptors introduction of an ionic lock between the cytoplasmic ends of helices 3 and 6 by a L6.30(275)E mutation inactivates the m opioid receptor and reduces the constitutive activity of its Thr6.34(279)K mutant. Biochemistry 41, 11972-11980. 

Two general classes of alkaloids are distinguished in ergot amine alkaloids and amino acid alkaloids (table 5.9) (Peroutka 1996). While the amine alkaloids are selective for antagonist effects on serotonin receptors, the amino acid alkaloids are less selective and act upon other monoamine receptors. The constituents of interest for cognitive enhancement are predominantly the amine alkaloids. 

This model detects both agonists and antagonists at monoamine receptors. 

The 5-H T3 receptor is the only monoamine receptor coupled to an ion channel, probably a Ca " channel. It is found in the cortex, hippocampus, and area postrema. It is typically localized presynaptically and regulates neurotransmitter release. Well-known antagonists are the potent antiemetics ondansetron and granisetron. 

Wachtel, H. and Schneider, H.H. (1986) Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors. Neuropharmacology 25(10) 1119-1169. 

The 5-HT3 receptor differs from other monoamine receptor subtypes in constituting a multiunit ion channel analogous to nicotinic acetylcholine, G ABA,, ... 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

FIGURE 5—60. The monoamine receptor hypothesis of depression posits that something is wrong with the receptors for the key monoamine neurotransmitters. Thus, according to this theory, an abnormality in the receptors for monoamine neurotransmitters leads to depression. Such a disturbance in neurotransmitter receptors may be caused by depletion of monoamine neurotransmitters, by abnormalities in the receptors themselves, or by some problem with signal transduction of the neurotransmitter s message from the receptor to other downstream events. Depicted here is the normal monoamine neuron with the normal amount of monoamine neurottansmitter and the normal amount of correctly functioning monoamine receptors. 

Perhaps a similar situation exists for depression due to a hypothesized problem within the molecular events distal to the receptor. Thus, second messenger systems leading to the formation of intracellular transcription factors that control gene regulation could be the site of deficient functioning of monoamine systems. This is the subject of much current research into the potential molecular basis of affective disorders. This hypothesis suggests some form of molecularly mediated deficiency in monoamines that is distal to the monoamines themselves and their receptors despite apparently normal levels of monoamines and numbers of monoamine receptors. 

The monoamine receptor hypothesis of depression suggests that depression is caused predominantly by an absence of key monoamine receptors in the brain. 

Sobarzo-Sanchez EM, Arbaoui J, Protais P, Cassels BK (2000) Halogenated Boldine Derivatives with Enhanced Monoamine Receptor Selectivity. J Nat Prod 63 480... 

In the laboratory, receptor studies have shown no significant activity at more than 40 receptor sites on nerve cells and other tissues, including the monoamine receptors usually involved in producing the effects of... 

Subsequently attention switched to neurotransmitter receptors in the 1970s and the monoamine hypothesis was reformulated in terms of monoamine receptors. It was found in animal experiments that several antidepressants reduced the density of beta-adrenoceptors (a type of noradrenalin receptor) in the brain after about two weeks of treatment. 

Joyce JN, Goldsmith SG, Gurevich EV. 1997. Limbic circuits and monoamine receptors Dissecting the effects of antipsychotics from disease processes. J Psychiatr Res 31 197-217. 

---