International Journal of Pharmacology Research
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Vol 2|Issue 2| 2012 | 88-108. ISSN 2249 - 7641 Print ISSN 2249 - 765X International Journal of Pharmacology Research www.ijprjournal.org AUTOPHARMACOLOGY- A REVIEW Saravana Kumar A*, Gandhimathi R *Department of Pharmacology, Sri Venkateswara College of Pharmacy, RVS Nagar, Chittoor, Andhra Pradesh, India. ABSTRACT Autopharmacology relates to the scientific study of the regulation of body functions by the activity of its naturally existent (or endogenous) chemical factors of the tissues. A more restricted definition would consider substances that were first identified as external agents which had a documented action on physiological functions, but later were discovered as existing as endogenous factors. The best example is the class of endorphins, which, as it name implies, were discovered to exist in the brain and have specific receptors in it, by investigations on the mechanism of action of opioids, such as morphine. A research area where autopharmacology principles assumed great importance was that of pain and inflammation, due to the great number of endogenous messengers, transmitters and modulators involved in their complex response at molecular and cellular level. Therefore the present review focused on endogenous substances that could fall under the concept of autopharmacology. Keywords: Autopharmacology, Endogenous substances, Body functions. INTRODUCTION Angiotensin Historically, the first approach to the concept of Secretin autopharmacology began with British physiologist and Gastrin pharmacologist Henry Dale in the 1910s, discovered the Cholecystokinin role of acetylcholine in synaptic transmission, and later Histamine proved by Austrian physiologist Otto Loewi, to be the Cannabinoids neurotransmitter involved in the proximal synapses of the Substance P autonomic nervous system (initially named Vagusstoff by The main scientific criterion for an Loewi, and later identified as acetylcholine). The same autopharmacological agent is the discovery of specific happened to another autonomic neurotransmitter, membrane receptors for it and, hopefully, its transduction noradrenaline (Akzeleransstoff by Loewi), which later and cell signaling mechanisms. proved to be chemically similar to a long used pharmacological agent, adrenaline, a hormone secreted by ENDORPHIN the adrenal glands. Both scientists were awarded the 1936 Endorphins (endogenous morphine) are Nobel Prize for Physiology or Medicine for their pioneering endogenous opioid peptides that function as and important contributions [1]. neurotransmitters. They are produced by the pituitary gland Endogenous substances that could fall under the and the hypothalamus in vertebrates during exercise, concept of autopharmacology are: excitement, pain, consumption of spicy food, love and Endorphins orgasm, and they resemble the opiates in their abilities to Dynorphin produce analgesia and a feeling of well-being. Bradykinin The term implies a pharmacological activity Prostaglandins Corresponding Author:- Saravana Kumar A EMail ID: [email protected] 88 | P a g e Vol 2|Issue 2| 2012 | 88-108. (analogous to the activity of the corticosteroid category of dopamine pathways, causing more dopamine to be released. biochemicals) as opposed to a specific chemical By hijacking this process, exogenous opioids cause formulation. It consists of two parts: endo- and -orphin; inappropriate dopamine release, and lead to aberrant these are short forms of the words endogenous and synaptic plasticity, which causes dependency. Opioid morphine, intended to mean a morphine-like substance receptors have many other and more important roles in the originating from within the body. brain and periphery however, modulating pain, cardiac, The term endorphin rush has been adopted in gastric and vascular function as well as possibly panic and popular speech to refer to feelings of exhilaration brought satiation, and receptors are often found at postsynaptic on by pain, danger, or other forms of stress, supposedly due locations as well as presynaptically. to the influence of endorphins. When a nerve impulse reaches the spinal cord, endorphins that prevent nerve cells Activity from releasing more pain signals are released. Immediately Scientists sometimes debate whether specific after injury, endorphins allow animals to feel a sense of activities release measurable levels of endorphins. Much of power and control over themselves that allows them to the current data comes from animal models which may not persist with activity for an extended time [2]. be relevant to humans. The studies that do involve humans often measure endorphin plasma levels, which do not History necessarily correlate with levels in the central nervous Opioid neuropeptides were first discovered in system. Other studies use a blanket opioid antagonist 1974 by two independent groups of investigators: (usually naloxone) to indirectly measure the release of John Hughes and Hans Kosterlitz of Scotland isolated — endorphins by observing the changes that occur when any from the brain of a pig — what some called enkephalins endorphin activity that might be present is blocked [4]. (from the Greek εγκέφαλος, cerebrum). Around the same time, in the calf brain, Rabi Runner's high Simantov and Solomon H. Snyder of the United States A publicized effect of endorphin production is the found what Eric Simon (who independently discovered so-called runner's high, which is said to occur when opioid receptors in the brain) later termed endorphin by an strenuous exercise takes a person over a threshold that abbreviation of endogenous morphine, meaning morphine activates endorphin production. Endorphins are released produced naturally in the body. Importantly, recent studies during long, continuous workouts, when the level of have demonstrated that diverse animal and human tissues intensity is between moderate and high, and breathing is are in fact capable of producing morphine itself, which is difficult. This also corresponds with the time that muscles not a peptide. use up their stored glycogen. During a release of endorphins, the person may be exposed to bodily harm Mechanism of action from strenuous bodily functions after going past his or her β-Endorphin is released into blood from the body's physical limit. This means that runners can keep pituitary gland and into the spinal cord and brain from running despite pain, continuously surpassing what they hypothalamic neurons. The β-endorphin that is released into otherwise would consider to be their limit. Runner's high the blood cannot enter the brain in large quantities because has also been known to create feelings of euphoria and of the blood–brain barrier, so the physiological importance happiness. of the β-endorphin that can be measured in the blood is far Runner's high has been suggested to have from clear. β-Endorphin is a cleavage product of pro- evolutionary roots based on the theory that it helped with opiomelanocortin (POMC), which is also the precursor the survival of early humans. Runner's high allows humans hormone for adrenocorticotrophic hormone (ACTH). The to run for vast lengths without pain. Most early humans behavioural effects of β-endorphin are exerted by its actions hunted and gathered for their food. This required them to in the brain and spinal cord, and it is presumed that the cover long distances hunting down their prey or foraging hypothalamic neurons are the major source of β-endorphin for their food. This could have caused them to develop at these sites. In situations where the level of ACTH is conditions such as shin splints and stress fractures in their increased (e.g., Cushing’s syndrome), the level of shin and feet bones. Without runner's high to negate the endorphins also increases slightly [3]. pain caused by running on bones with these conditions, β-Endorphin has the highest affinity for the μ1 early humans theoretically would not have been able to opioid receptor, slightly lower affinity for the μ2 and δ repeatedly cover these vast distances in search of their food opioid receptors, and low affinity for the κ1 opioid and thus would have starved. Current African tribes make receptors. μ-Opioid receptors are the main receptor through use of runner's high when conducting persistence hunting (a which morphine acts. In the classical sense, μ opioid method in which tribesman hunt an animal and track it for receptors are presynaptic, and inhibit neurotransmitter miles, eventually killing the animal due to its vulnerability release; through this mechanism, they inhibit the release of brought on by exhaustion) [5]. the inhibitory neurotransmitter GABA, and disinhibit the 89 | P a g e Vol 2|Issue 2| 2012 | 88-108. In 2008, researchers in Germany reported on the Relaxation mechanisms that cause the runner's high. Using PET scans In 2003, clinical researchers reported that combined with recently available chemicals that reveal profound relaxation in a float tank triggers the production endorphins in the brain, they were able to compare runners’ of endorphins. This explains the pain relief experienced brains before and after a run. during float sessions. It is also suggested by many that endorphins are some of the many chemicals that contribute to runner's Acupuncture high; other candidates include epinephrine, serotonin, and In 1999, clinical researchers reported that inserting dopamine. Previous research on the role of endorphins in acupuncture needles into specific body points triggers the producing runner's high questioned the mechanisms at production of endorphins.