Opiates, natural

The main objective of this experiment was to demonstrate that a peptide lead compound could be used in rational design of a non-peptide library. One of the natural opiates, met-enkephalin, is used as a hypothetical lead compound. The averaged frequency distribution based on four SA runs is obtained (data not shown). Based on this result, 03 had the highest frequency, and the frequencies of A4, Dll, D13, D14, D16, D2, D3, D5, and D9 are also above random expectation. Apparently, 03 appeared in all the reported active peptoids with opioid activity (cf. Table 1). Comparison of the structure of met-enkephalin (Fig. 5) with 03 indicated that 03 is similar to the side chain of tyrosine, which is the N-terminal residue of met-enkephalin. Among other building blocks found more frequently than random expectation, A4, D3, and D13 are present in the reported opioid peptoids (cf. Table 1). Thus, the SA sampling correctly identified four... 

Rigid Geometry Studies of Enkephalin The enkephalins are linear pentapeptides, H-Tyr-Gly-Gly-Phe-Met-NH2 (see Figure 2a.) and H-Tyr-Gly-Gly-Phe-Leu-NH2, which bind to several classes of opiate receptors in the mammalian brain including the same receptor as morphine(26,27). Enkephalins have drawn the interest of theoretical biophysicists for two reasons. First, because of their natural opiate activity, it is hoped that improved analgesics can be developed. Second, as pentapeptides, enkephalins are small enough that the molecule can be examined theoretically without excessive expense of computer time. 

It has been shown that after stress or injury, the brain produces and releases its own natural version of opiates to control pain and ease anxiety. People with PTSD continue to produce elevated levels of natural opiates after the trauma has passed. In addition, there exists an increased use of heroin and other opiate-based drugs of abuse among patients with PTSD. Once more, it is difficult to determine whether these elevated natural opiates existed before the disorder developed. 

There are many legal medicines that use opiates or opiate-like substances. Most of the opiate-based medicines used today are not made from natural opiates, but are either synthetic or semi-synthetic. Synthetic opiate drugs are not actually opiates at all they are merely different chemicals that act like opiates. Semi-synthetics are those drugs that involve changing the chemical structure of a natural opiate. An example of this is heroin, which is a human-made variation of morphine. Morphine and codeine are the principal natural opiates used as medicines and what follows are descriptions of the other most frequently used opiate-based medicines. 

Naloxone is an opiate antagonist which is used as an antidote to opiate overdoses. It has also been used in withdrawal programs, for babies born to addicted mothers, and in the study of the body s natural opiates, the endorphins and enkephalins. 

Hydromorphone and its natural opioid relatives have been used to relieve pain, treat a variety of ailments, and create euphoric feelings at least as far back as the time of the ancient Greeks. In early Greek history, the priests controlled the use of opium and ascribed to it supernatural powers. In the fifth century bc, Hippocrates, the father of medicine, dismissed the supernatural attributes of opium. Hippocrates believed opium had cathartic, narcotic, hypnotic, and styptic properties. He believed that all diseases had a natural origin and could be cured by natural therapies. All of the natural opiates historically were derived from opium poppy plants. The liquid extracted from the poppy seeds was typically dried to create a concentrated powder. These extracts were then smoked, eaten, or drank. 

Morphinans bearing a 6-oxygen function have proved to be a valuable source of precursors for the synthesis of natural opiates/53,55 58 Compounds such as dihydrothebainone (64, R = OMe R = H) may be derived from thebaine, whereas others are totally synthetic/8 ... 

Callaghan R, Riordan JR. 1993. Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells. J. Biol. Client. 268 16059-64... 

Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells... 

Many short-chain peptides are important biochemicals. For example, enkephalins and endorphins (Figure 15.12) are referred to as natural opiates because they moderate pain in the same manner as opium derivatives. Our bodies synthesize enkephalins and endorphins to moderate pain, and our pain threshold is related to levels of these neuropeptides in our central nervous system. Individuals with a high tolerance for pain produce more of these neuropeptides and consequently tie up more receptor sites than normal hence, they feel less pain. A dose of heroin temporarily bonds to a high percentage of the sites, resulting in httle or no pain. Gontinued use of heroin causes the body to reduce or cease its production of enkephalins and endorphins. If use of the narcotic is stopped, the receptor sites become empty, and withdrawal symptoms occur. 

FIGURE 15.12 Enkephalins and endorphins, polypeptides that are natural opiates. Note that all three polypeptides have one identical amino acid sequence. 

It was found that the effects of these opiate-like substances could be rapidly reversed by administration of the morphine antagonist naloxone and this and other findings led to the conclusion that the enkephalins and endorphins bind to the same receptors in the central nervous system, of which there appear to be at least three types, as morphine itself. Evidence was also obtained that the natural opiates may play a part in normal emotional responses as well as in the control of pain perception. The natural opiates differ fi om morphine and its derivatives in that they do not accumulate and lead to the tolerance which occurs with morphine. It has been suggested that the effects of acupuncture may result from the release of natural opiates. 

Opiates are drugs naturally found in the opium Poppy Papaver Sonnfferum, and opioids are semi-synthetic drugs prepared from the natural opiates. Both act on the central nervous system producing cough suppression, analgesia, euphoria, sedation, respiratory depression and arrest, nausea, confusion, unconsciousness, coma, and addiction. In 2007, the number of opioid users in Europe was estimated between 1.2 and 1.5 million people (2). 

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