Antagonist Synthesis Essay

1998. Effects of local anesthetics on Na+ channels containing the equine Hyperkalemic periodic paralysis mutation. American Journal of Physiology. 275(2): C389-C400.

Acetylcholine is found at the peripheral nervous system and synapses in the central nervous system within the human body. Acetylcholine is an excitatory neurotransmitter that conducts electrical impulses, allowing nerve cells to communicate with muscle cells and generate muscle contractions. However, acetylcholine produces an inhibitory effect in cardiac muscle. (Waymire, 1997) Therefore, once the Daphnia are exposed to acetylcholine, their heart rate is expected to decline. In contrast, epinephrine, also known as adrenaline, is a hormone which binds to the beta adrenergic receptors in the heart leading to increases in the firing rate of the pacemaker cells. (Meyers, 2011) Therefore, the Daphnia’s heart rate is expected to increase with exposure to

It inhibits Na+K+ ATPase active transport raising cytosolic Na+ concentrtion and leading to the increasement of Ca2+ concentration in the sarcoplasmic reticulum by the reversival exchange of Na+ and Ca2+ in the myocardial cell. This increase in the contraction of the heart (32) and improve cardiac outpur , left ventricualr ejection fraction, stroke volume, pulmonary capilary wedge pressure and exercise tolerance (33). Secondly, digoxin produce vagus activation showing negavite chronotropic action in SA node and negative dromotropic action in AV node. This lead to a shift in automatic balance by dominating the positive iontropic action of the drugs digoxin (33). In this way digoxin is cosinder as a only available inotropic drug which increase cardiac output and decreae pulmoary capillary wedge preure with our increasing heart rate and without decreasing blood pressure

Ach binding to nicotinic receptors has an excitatory effect because it result in the direct opening of the Na channel and the production of action potential (VanPutte, Cinnamon L., and Rod R. Seeley). When Ach binds to The muscarinic receptor, the cell response is mediated through G proteins the response is either excitatory or inhibitory, depending on the effectors.( VanPutte, Cinnamon L., and Rod R. Seeley)

The search for a new anti-migraine drug was started by Glaxo in 1972. In the 1960s, studies showed that vasoconstriction from 5-HT, ergotamine and nor-adrenaline could reduce migraine attacks. Research also showed that platelet 5-HT level reduces during migraine attacks. Many side-effects were associated with the use of 5-HT as a drug and then scientists started research on the receptors of 5-HT in order to discover and develop a more specific agonist for 5-HT receptors. Research on the 5-HT receptors and their effect led to discovery of several types and subtypes of 5-HT. AH24167 showed a vasodilatory effect instead of vasoconstrictory due to the agonist effect on another type of 5-HT receptors later assigned the name 5-HT7. AH25086 was the second compound developed and showed a vasoconstrictory effect but was not released as a drug due to low per oral bioavailability.

The new drug blocks the sodium channel 1.7 according to the channel's level of activity - the more active the channel is the stronger will be the drugs hampering effect. Current drugs, in comparison, block the sodium channels without accounting for the activity level, which results in unecessary side effects. Sodium channels are located in nerve cell membranes. Their activation triggers the sensation of pain, the severity of which is proportional to the channels' activity level. According to the Zurich researchers, trigeminal neuralgia is believed to stem from a nerve deficiency or damage at the base of the skull. Given that local injections cannot reach this region, drugs are the first line of defense against the

The use of a vasopressor in short exposure, usually no more than nine hours at a rate of .51 micrograms/kg/min. Norepinephrine, an alpha 1 and 2 receptor, is a vasoconstrictor being used to treat hypotension that is not responding to fluid replacement, in turn not regulation the mean arterial pressure. NE given to reduce the symptoms of sepsis shock due to being a Beta 1 activator. Adverse effects of NE alter heart rate or rhythm, cause angina and possible overdose if maximum dose limit is exceeded. (Girard, Opal & Ely, 2005)

The PNS decreases heart rate by transmitting its impulses onto long, myelinated preganglionic neurons that trigger the release of ACh onto nicotinic cholinergic receptors found on the postganglionic cell. The impulse then travels along short, unmyelinated cholinergic postganglionic neurons, and triggers the release of ACh onto muscarinic cholinergic receptors found on the effector target cells. The speed and duration of response by the PNS is quicker because most of its axonal journey is done upon long myelinated fibers. The PNS release of ACh can also be easily broken down by acetycholinesterase, so its effect only last for a short period of time. The speed and duration of response by the SNS is slower and longer due to most of its axonal journey being done upon long

appears to be a discrepancy between its weak affinity for opioid receptors and its potent

f) Account for the response to acetylcholine in the two preparations. Which receptor(s) mediates the effects of acetylcholine in the rings with and without endothelium?

Since the evolution of H2S as an essential gasotransmitter at cellular level, and based on the fact that H2S characteristically similar to NO; researchers aimed to investigate the physiological effects of H2S on cardiovascular system, proposing that H2S donors may become a potential treatment for various cardiovascular abnormalities including atherosclerosis, hypertension, vasoconstriction and cellular apoptosis induced by reactive oxygen species [24-26]. The cellular mechanism by which H2S induce cardiovascular effects is not well illustrated yet. A recent study suggested that H2S can reduce heart rate and blood pressure through KATP channel activation when intracerebroventricular NaHS (H2S donor) significantly reduced the blood pressure and heart rate of experimental rats, while Glibenclamide, a potent KATP channel blocker, effectively attenuated and reversed the effect of NaHS on heart rate and blood pressure [38].

The rat phrenic nerve preparation is very useful as it teaches us not only a lot about neuro muscular and muscle physiology but also the pharmacodynamics of different drugs such as neuromuscular blocking agents and determining their potency at blocking the neuromuscular junction. This preparation was originally used for the bioassay of tubocurarine (Bülbring et al, 1997). However there are a few limitations to this prep, for example it is hard to differentiate between the different neuromuscular blockers, whether they are depolarizers or non-depolarizers because depolarizers fail to reverse the effects of non-depolarizers. As a result of this, another prep is preferred namely the chick sciatic nerve-tibialis anticus muscle (Vogel, 2013).

The nervous system of the human body is composed of two units; the central nervous system and the peripheral nervous system. To get to the focus of this paper, which encompasses the pharmacology of the sympathetic and parasympathetic nervous system, it must be understood that the peripheral nervous system further breaks down into motor and sensory neurons, and the motor neurons even further breakdown into the somatic and autonomic nervous system. The autonomic nervous system is then divided into the sympathetic division and parasympathetic divisions which, “controls involuntary responses by influencing organs, glands and smooth muscle”. (68, book). The parasympathetic and sympathetic divisions have actions that oppose each other and the drugs used for each reflect this in how they interact with the body. Depending on the reaction that is wanted from a particular drug used, there are also considerations that need to be addressed prior to make sure the right reaction will occur. Although they are small divisions of the peripheral nervous system, the sympathetic and parasympathetic divisions are vital to the nervous system and the human body as a whole.

Next, they injected 0.10 mL of 1/ 2,500 acetylcholine and noted its response. Students were asked to observe the rabbits pupil with good light and injected 1mL of 1% atropine through the IV drip over the course of seven to ten minutes. Students were asked to investigate the rabbit’s pupils again to observe if they were maximally dilated. Next, they stimulated the caudal end of the right vagus once more with twice the amount of voltage and recorded the results. An injection was given of 3mL of 1/ 2,500 acetylcholine and observed how the blood pressure was effected.

The understanding and studying of the GPCR structure is very important for designing the right drugs. Studies have shown that some of the GPCRs are not pоtential drug targets because their physiological function cannot be related to disease. Such GPCRs include the sensоry (olfactory, taste) receptоrs and thus, leave 369 GPCRs that are pоtential drug targets (Gloriam et al., 2007). 46 of these are being targeted successfully by drugs – the rhodopsin-, secretin- and glutamate-like receptor families. β-adrenergic, angiotensin II and vasopressin receptors are examples of GPCRs that are lоcated in the membranes of cardiac cells and play key role in regulatiоn of the cardiac functiоn (for example, cardiac muscle contractility, blood pressure, etc.).