Free Experimental Proposal Dissertation Proposal Sample

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Abstract
Cocaine has a variety of physiological manifestations. Cocaine is a local anesthetic that was discovered in the sixteenth century. The characteristic of being a local anesthetic is the primary attribute for its application in medicine. There are a number of compounds that have been recently created that are more effective than cocaine for the purposes of anesthesia. Cocaine also has the characteristic of being a potent vascoconstrictant. The applications of vascoconstrictant are effective for the implementation of throat and nose surgery. The application of cocaine in the nose and throat areas has the characteristic of deterring bleeding. Cocaine also has influence over the sympathetic nervous system; it has been well documented with regards to increasing the heart index and the sanguine pressure. Cocaine also produces a perception of euphoria in the consumer (Lemke and Williams, 2008).
Cocaine possesses several areas of action that take place in the central nervous system. Cocaine has been demonstrated to impede the reuptake of the substance designated as norepinephrine (NE) dopamine ((DA) and serotonin (5- HT), in addition cocaine reacts on the σ receptors and the cholinergic muscarinic. There could be a combination of any of these sites that could be applied in order to medicate the abuse of the dopamine uptake. This activity has the outcome of an accumulation of dopamine in the area of the synaptic cleft. This accumulation derives the dopaminergic transmission. The strengthening of this effect is the causal attribute of the characteristics of cocaine. This strengthening effect is in addition to the perceptions of euphoria that it elicits (Carroll et al., 1991).
The mesolimibical conduit has been correlated with the strengthening effects of cocaine, especially the dopaminergic nerve connections located in the nucleus accumbens of the area of the prefrontal cortex. The binding that takes place with the dopamine receptors modifies the function condition of the limbic zones that cause the manifestations of cocaine ingestion. This is regarded as the foundation for the dopamine hypothesis. The assertions that are included in the dopamine hypothesis include the following:
- The strength of the diverse cocaine related mixtures in the sustenance of the self-administration can be forecasted by each of the mixtures’ tendencies of the dopamine transporter. The strength of the desire for self-administration cannot be forecasted by the compound’s tendency for the serotonin or the norepinephrine transporters.
- The lesion where the dopamine enervation has taken place in the nucleus accumbens has the outcome of disrupting the self – management of cocaine. The lesions that are present in the dopaminergic terminal or the lesions that are manifested by the nonadregenic system located in the stratum are not without the same effect.
- The craving of cocaine in humans is diminished by the agonist of dopamine that is indirectly applied.
- The enhancement of the levels of extra dopamine that are present in the brain subsequent to ingestion have a temporal course that is in alignment with the temporal course that is the duration of the period of euphoria (Carroll et al., 1991).
The structural activity correlation for cocaine and the analog connecting of the serotonin, norepinephrine, and dopamine transporters were ascertained. The cocaine inhibition of the ligand binding to all of the serotonin, dopamine and norepinephrine sites possesses a stereo particular requisite for the levorotary isotomer. The binding capacities of cocaine based derivations that applied the N- substitution C3 and C2 constitution modifications demonstrated distinction s in the structure action correlation for cocaine at the transport locations. The extraction of the N- methyl groups demonstrated a slight change in the binding capacity for the dopamine transporter site. Notwithstanding, the extraction of the N- methyl group demonstrates enhancements at the location of the serotonin transporter and the norepinephrine sites. The modifications in the formation at the C2 substitution demonstrated modifications in the binding capacity of the dopamine transporter (Ritz, 1990).
The bacteriologically based CocE is a serine hydrolase that has the characteristics of α- β that is encountered in the bacterium that is designated as Rhodoccocus special strain MB1. This bacterium is encountered in the soil samples that are in the vicinity of the coca plant. The CocE has the qualities of being the most effective naturally formed hydrolase and transforms the cocaine into the physiologically inert substances that are designated as benzoic acid, methyl ester and ecgonine. The CocE has been applied in rodent experiments and is detailed to provide a reversal of the toxic, neurological and cardiovascular manifestations of cocaine. The CocE demonstrates a half – life of about ten minutes at a temperature of 37° C. (Brim et al., 2012).
Introduction
The drug that is being researched is cocaine. There are three distinct cell receptors that are categorized as neurotransmitters that are influenced by the drug. The first neurotransmitter is dopamine. The second neurotransmitter is serotonin. The third neurotransmitter is norepinephrine. As the dopamine is liberated in the brain, cocaine has the characteristic of being a dopamine inhibitor by its reabsorbing the dopamine containers after they have completed their endeavor. The cocaine causes the dopamine to become trapped in the brain and causes the consumer a feeling of euphoria. Cocaine also influences the serotonin in the brain. The serotonin has the impact of deterring a person’s, hunger, body temperature, affective state and sleeping cycles. The last characteristic that cocaine influences is norepinephrine that has effect on the body’s flight or fight responses. Cocaine influences the metabolism by means of the heart rate, the liberation of glucose and the blood circulation to the musculoskeletal system (Carroll et al., 1991).
Experiment 1
The goal of this experiment is to review the effectiveness of cocaine by applying a rectal suppository that distributes the cocaine into the anal area. The cocaine that is delivered could be delivered by means of a plastic suppository. The difference in the ingestion with plastic suppository is that the subtle liquid media is brought into the anal areas by the application of a plastic suppository. The cocaine is placed into a pressurized aerosol container. The patient would insert the suppository into the anal cavity. In the rectal plastic suppository paradigm, the cocaine would be directly inserted into the anal area by means of the application of a liquid form (Integrated Pharmacy Care Laboratories, 2014).
Method
In this empirical test, twenty respondents were applied in order to form the experimental group. The respondent varied in ages from eighteen to forty years old. All of the participants are suffering from moderate pain, chronic pain or acute pain. The control section of the experiment will be composed of twenty participants who range from eighteen years of age to forty years old. All of the participants in the control group and the experimental group are suffering from acute, moderate or chronic pain. The participants in the control group will be administered a placebo and the participants in the experimental group will be administered cocaine. The hypothesis of this experiment is that the rectal suppository is a more efficient form of delivering the opioid cocaine into the body that causes the relief of pain in seconds after its ingestion. There are a number of people who are suffering from moderate, acute or chromic pain that would benefit from the application of cocaine in nebulizer form (Integrated Pharmaceutical Care, 2014).
Results
The participants in the experimental group that implemented the use of the rectal suppository demonstrated more effective reports of pain relief that the participants who were administered a placebo. There were twenty respondents who documented their relief from pain in comparison to none of the participants from the control group.
Experiment 2
The second experiment is based on the experiments that were performed with rats with regards to the intravenous ingestion of cocaine. The aim of the experiment is to review the outcomes of self-administration of cocaine by intravenous injection by applying the rats as laboratory test respondents. The intravenous injection of cocaine is hazardous to humans. This is the reasons that the rats were used in the original experiment. The empirical study will be performed in order to contribute to the body of knowledge with regards to the effects of the intravenous ingestion of cocaine. The hypothesis is if the rats will develop a dependency on the cocaine injections (Festing, 2011; Koek et al., 1988).
Method
At first, a model was produced that enabled the rats to self-administer the cocaine into their bodies by means of an intravenous catheter. The researchers performed the first injections with regards to the dosages of cocaine. The response of the rats was examined immediately after the injections. The objective of the primary administration of the cocaine by the empiricists was to review if the rats would self-administer the cocaine dosages as an outcome of the dependency that was caused (Festing, 2011; Koek et al., 1988).
Results
The results showed that the implementation of a method of self-administration for the rats with regards to the cocaine injections would produce a dependency on the cocaine. The rats behaved chaotically after the injections. Some of the rat tried to escape from the cages instead of self-administering the cocaine. There were other rats who tried to remove the intravenous catheter. One of the rats self-administered the cocaine dosages. In the course of two weeks, the rat that administered the dosages of cocaine intravenously died (Festing, 2011; Koek et al., 1988).
The rats developed a drug dependency to the cocaine. The cocaine caused the rats to produce psycho toxicity. The empirical test showed that the biological characteristics of the rats were identical to the theoretical repossess of human beings. The findings from the experiment were that although it is more efficient to inject the cocaine directly into the blood stream and bypass the blood- brain barrier, the rats injected the cocaine as a result of the increase dependency that was caused by the intravenous injection of the cocaine. The cocaine injections were the causal attributes of the rats exhibiting a physical and psychological dependency. The significance of the experiment and the verification of the hypothesis was that a drug dependency was caused and the symptoms that the rats displayed were those of the opioid triads. The significance of the empirical test was to instruct empiricist on the manner by which the psychological intervention could be applied in order to deter individuals from developing addictions to cocaine (Carroll et al., 1991).
Experiment 3
Ingesting cocaine vaginally supplies a method that provides a dependable and quick method of cocaine delivery that can be conducted together with other compounds. The vaginal ingestion of cocaine can achieve the system wide distribution of the cocaine dosages while bypassing the liver and the blood brain barriers. The therapeutic effect of the cocaine dosages that are ingested orally is decreased. In the vaginal suppository application of cocaine, a new insight into the functioning of cocaine will be attained with regards to the dosages that can be administered vaginally with the analgesic drug. The hypothesis that will be examined is the ingestion of cocaine by means of a vaginal suppository more efficient and less toxic form of cocaine delivery for acute, chronic and moderate pain sufferers (Integrated Pharmaceutical Care, 2014)).
Method
An experimental collection of participants was selected. The number of participants that were included in the experimental group was restricted to twenty. The numbers of the respondents in the experimental collection of participants was restricted to twenty. All of the members of the control and the experimental collection of participants were individuals who suffer from acute, moderate and chronic pain. A control collection of participants was also formulated with twenty participants. All of the participants in the control and the experimental collection of participants were individuals who were aged between eighteen and forty years of age. The participants of the experimental group were delegated vaginal suppositories that possessed small amounts of cocaine. The members of the control group were given a placebo (Carroll et al., 1991).
Results
The development of a vaginal suppository form of cocaine ingestion supplies an improved method of enhancing the analgesic qualities of cocaine. The vaginal suppository model was applied in order to enable a quick response of the cocaine dosages that were ingested by the participants. The analgesic effect that takes place with the cocaine occurs in the nerve administration centers of the medulla. The relief of pain occurs with a lesser dosage than what would be required for oral administration. In oral form, a dosage of 35 mg was required in order to provide effect s of pain relief. The amount of cocaine that was administered in the vaginal suppository was less than 10 mg (Integrated Pharmaceutical Care, 2014).The participants who were given the cocaine in the form of a vaginal suppository showed much better outcomes than the participants who were given the placebo (Carroll et al., 1991). In the experimental group of participants, the participant documented that they perceived immediate relief from the pain that they were experiencing. The hypothesis of the effectiveness of the vaginal suppository has been confirmed.
Conclusion
The three paradigms of cocaine ingestion that were applied in the three experiments a have been confirmed to be more effective than the oral ingestion of liquid cocaine. In the oral ingestion of cocaine, the cocaine must pass through the digestive system and the liver. In the liver, a large amount of the cocaine is eliminated from the body in the form of urine e and bile. The three methods of directly applying the cocaine dosages provide an effective form of administration to the body. These empirical studies are significant with regards to the comprehension of the function of the enzymes in the liver and the hepatic system, with regards to the metabolizing of cocaine.
Appendix
Figure 1: Chemical Structure of Cocaine
https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcRAAMmNe23htVlthYRfaM881qmCqX5DIk8N1f93vg6mbE0TrSSt
Figure 2: Diagram of Cocaine Mechanism
http://tmedweb.tulane.edu/pharmwiki/lib/exe/fetch.php/cocaine3.png?
Appendix
Figure 3: Steps of Orally Ingested Cocaine Decomposition in the Liver
http://www.cell.com/cms/attachment/577032/4297916/gr2.gif
References
Brim, R. L., Noon, K. R., Collins. G. T., Stein. A., Nichols, J., Narisimhan, D.,& Sunahara, R. K. (2012). The fate of bacterial cocaine esterase (CocE): An in vivo study of CocE- mediated cocaine hydrolysis CocE pharmakinetics and CocE elimination. The Journal of Pharmacology and Experimental Therapeutics, 340(1): 83- 95.
Carroll, F.I., Lewin, A. H., Boja, J. W. and Kubar, M. J. (1991) Cocaine receptor: Biochemical characterization and structure activity relationships pf cocaine analogues at the dopamine transporter. Journal of Medicinal Chemistry, 35(6): 969- 971.
Festing, M. F. W. (2011). How to reduce the number of animals used in research by improving experimental design and statistics. ANZCART Fact Sheet 10.
Integrated Pharmaceutical Care Laboratories (2014). Routes of administration that utilize suppositories. Integrated Pharmaceutical Care Laboratories.
Koek, W., Woods, J. H. and Winger, J. D. (1988). MK – 801, a proposed non- competitive enlargement of excitory amino acid neurotransmission, produces phencyclidine like behavioral effects in pigeons, rats and Rhesus rats. JPET, 245(3): 969- 974.
Lemke, T.L. and Williams, D.A. (2008). Foye’s principles of medicinal chemistry (6th edition). Philadelphia, PA: Wolters Kluwer│ Lippincott, Williams and Wilkins.
Ritz, M. C. Cone, E. J., and Kuhar, M. J. (1990). Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: A structure activity study. Life Sciences, 46(9): 635- 645.

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