Serotonin receptor blockers

Migraine was a condition that was refractory to treatment until the discovery of the serotonin receptor blocker, such as sumatriptan. This agent was soon followed by several other drugs that acted by the same mechanism. Tidembersat (13) a compound more closely related, both in structure and mechanism of action, to antihypertensive benzopyrans that act on... 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

The answer is a. (Hardman, pp 228-229.) Phentolamine is a non-selective a-adrenergic receptor blocker (i.e., it has affinity for both - and ct2-adrenergic receptor sites). It also has a prominent direct relaxant (musculotropic spasmolytic) effect on arterioles, which results in vasodilation and reflex tachycardia. In addition, phentolamine can block the effects of serotonin and will increase hydrochloric acid and pepsin secretion from the stomach. Phentolamine is used for the short-term control of hypertension in patients with pheochromocytoma (i.e., a type of secondary hypertension) because of the high incidence of tachycardia associated with the compound, it is not used chronically for the treatment of essential hypertension... 

Apomorphine is a nonergot dopamine agonist given as a subcutaneous rescue injection. For patients with advanced PD with intermittent off episodes despite optimized therapy, subcutaneous apomorphine triggers an on response within 20 minutes, and duration of effect is up to 100 minutes. Most patients require 0.06 mg/kg. Prior to injection, patients should be premedicated with the antiemetic trimethobenzamide. It is contraindicated with the serotonin-3-receptor blockers (e.g., ondansetron). 

SSRI = selective serotonin reuptake inhibitor SNRI = serotonin norepinephrine reuptake inhibitor ARB = angiotensin receptor blocker ACE = angiotensin converting enzyme COX-2 = cyclooxygenase 2 ADHD = attention deficit hyperactivity disorder. 

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

Many of these drugs have effects that are not mediated by Hi-receptors (Table 38.2). The antimuscarinic activity of several first-generation Hj-blockers may account for their effectiveness in combating motion sickness and their limited ability to suppress parkinsonian symptoms. The phenothiazines have some capacity to block a-adrenoceptors, whereas cyproheptadine Periactin) is an antagonist at serotonin receptors. Diphenhydramine Benadryl), pyrilamine (Ryna), and promethazine Phen-ergan) are effective local anesthetics. Many second-generation antihistamines also have been found to inhibit the non-histamine-mediated release of various... 

Tramadol has about one tenth the pain-relieving ability of morphine.53 There are two enantiomers, and both contribute to pain relief, but via different mechanisms. (+)-Tramadol and the metabolite (+)-0-desmethy 1-tramadol, which is referred to as Ml, are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine re uptake.25 This latter action enhances the inhibitory effects on pain transmission in the spinal cord. Because the actions of the two enantiomers are complementary, they are usually supplied as a racemic mixture. However, because it is a serotonin-reuptake blocker, interaction with other medications can lead to the occurrence of serotonin syndrome.54... 

L-deprenyl (selegiline), a monoamine oxidase B inhibitor, clonidine and guanfacine, a2-adreno-receptor agonists, and levodopa (L-dopa) have been reported to improve cognitive function in some subjects. Zimeldine, citaloprani, and alaproclate — selective serotonin uptake blockers — have no beneficial effects. 

Adverse effects Hi receptor blockers have a low specificity, that is, they interact not only with histamine receptors but also with muscarinic cholinergic receptors, a-adrenergic receptors, and serotonin receptors (see Figure 40.6). The extent of interaction with these receptors and, as a result, the nature of the side effects, vary with the structure of the drug. Some side effects may be undesirable, and others may have therapeutic value. Furthermore, the incidence and severity of adverse reactions varies between individual subjects. 

Nefazodone (Serzone), like venlafaxine, is a new antidepressant that affects multiple neurotransmitter systems. Like trazodone, nefazodone is a potent 5-HT2A receptor blocker. In addition, it is both a serotonin and norepinephrine reuptake inhibitor. The most common side effects are nausea, headache, anxiety, sedation, and dizziness. Its use is contraindicated with Seldane, Hismanal, and Propulsid, and there is a warning regarding its use with Xanax. 

The antidepressants, generally, produce their therapeutic effects by blocking the reuptake of one or more catecholamines (norepinephrine, serotonin, and dopamine), which leads to a decrease (down-regulation) of the number of post-synaptic receptors—generally within seven to twenty-one days, coinciding with the onset of clinical effect (see chapter 3). The MAOIs block monoamine oxidase, which metabolizes the catecholamines stored at the nerve ending of the presynaptic neuron—thereby making more catecholamine available. Stimulants increase the release of catecholamines. Buspirone is a 5-HT lA receptor blocker. 

Mlrtazapine. The tetracyclic mirtazapine (Remenin) is another example of an or-antagonist that shows selectivity for 02 receptors versus serotonin receptors and at histamine H receptors. 

---