Drug Designing: Open Access
Open Access

Drug Discovery and Development Process in Analgesic Drugs

Thelma Mark^{* *}Correspondence: Thelma Mark, Department of Drug Discovery Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA, Email:

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Description

The process of finding chemical entities with the potential to be medicinal agents is known as drug discovery. The identification of novel molecular entities that may be useful in the treatment of diseases that meet the criteria for unmet medical needs is one of the main objectives of drug development programmes. These illnesses are either life-threatening or potentially fatal, and there are no proven effective treatments for them. Medication target types that are currently being marketed constitute a relatively small portion of all drug target types. Less than 50% of the medications on the market are directed at G-protein coupled receptors, nuclear (hormone) receptors, and ion channels. The majority of marketed medications—by far—are pharmaceuticals that target enzymes.

It may be required to expand into new categories of drug targets to address some therapeutic gaps, but doing so presents a significant intellectual barrier, especially when doing so in lesswell- researched categories of drug targets. There is a high attrition rate in the conventional pharmaceutical research and development process. Most estimates indicate that researchers will normally have used over 100 drug lead screens to narrow down candidates from tens of thousands of compounds for every new medicine introduced to the market. In addition to being expensive and time-consuming, lead chemical discovery research is both time and money-consuming, taking over five years and more than $200 million, according to some estimates.

Even when loaded with a potential lead chemical, compounds can nevertheless fail during the ensuing development phase for reasons that were unforeseeable during the lead discovery phase. Unacceptable toxicity, a lack of in vivo efficacy in disease models of interest, market and subpar biopharmaceutical properties can all be causes of failure. In addition, complexity of the synthetic material, limited potency, and unclear toxicological data can significantly hold down development. Therefore, carefully considered and applied drug discovery methodologies are required, especially when new therapeutic target or disease domains. In the past five years or so, a large number of potential targets for the discovery of novel analgesic drugs have surfaced, but few of them have a high probability of success until the drugs discovered have reached the stage of phase II clinical proof of concept due to our poor understanding of the pathophysiology of pain. The targets can be divided into three categories:

1. Modifications to an already-existing pharmacological mechanism.

2. A novel selective mechanism that results from a deeper comprehension of an existing analgesic drug's mechanism.

3. An whole new mechanism that results from basic biology research, human pathophysiology research, or genomic research.

The initial target has the most likelihood of success but may also have the lowest possibility of representing a true therapeutic advance. These strategies each have a separate cost-benefit analysis. There comes a point where the improvement is so slight that the treatment will not cover its development costs, even if improving already-available medications offers the highest likelihood of success.

A steady supply of new potential targets has been produced by advances in molecular neurobiology. The clinic has not yet received an analgesic using this strategy. Although adopting such targets is a high-risk strategy, transgenic mouse phenotyping in assays for pain and inflammation can offer early target confirmation. Finding receptor or ion channel targets that exhibit phenotypic alterations associated with the pathophysiology of human pain may lead to the development of therapies for pain syndromes that are resistant to currently available analgesics. Numerous possible novel targets have been directly discovered at the preclinical stage as a result of genomic research, including the use of gene subtraction techniques to identify changes in gene expression in diseased tissue after damage or inflammation. Predicting the physiological and pathological importance of novel targets as well as the possible benefits and drawbacks of drugs that act on the final protein products of these genes will be a difficult task.

The significance of this cannot be overstated given that there are likely to be more targets than can be successfully exploited and that the development of novel analgesics will depend more and more on the careful selection of the best targets. To do this, possible targets must be rigorously examined in light of data from preclinical and clinical sources, including information from transgenic animals, as well as data derived from the pharmacology of drugs used as analgesics.

Conclusion

The identification and assessment of subtypes and/or splice variants of targets discovered in clinical or preclinical investigations can be aided by information from genomic studies. For instance, drugs like carbamazepine, phenytoin, mexiletine, and amitriptyline that block sodium channels are some of the more efficient treatments for neuropathic pain.

These drugs' broad range of pharmacological actions and, more significantly, their non-selective targeting of sodium channel subtypes, which together produce a restricted therapeutic window, limit their therapeutic efficacy. One of the most significant translational scientific endeavours that improves human health and wellbeing is the discovery and development of new drugs. An overview of the drug discovery and development process, from the lab bench to postmarketing approval, is provided in this chapter. To put the current state of affairs and predicted developments in the near future into perspective, a brief history of drug discovery throughout the ages is included. Preclinical research, phase 1 through phase 4 clinical studies, lead molecule identification and optimization are all components of drug discovery.