Pharmacology of Opioids Classifications Opioids can be classified according to their mode of synthesis into alkaloids: semi-synthetic and synthetic compounds. Raw opium contains morphine and smaller amounts of codeine and simple chemical manipulations of these basic opiate alkaloids will yield a range of semi-synthetic opioids.
As noted in Drugs Behaviour and Society (Hart, Ksir, Hebb,Gilbert & Black, 2012) adding two acetyl groups to the morphine molecule results in Heroin. Heroin to readily penetrates the blood brain barrier making it two to three times more potent than morphine.
During the 20th century a number of synthetic opioids were also produced. These synthetic compounds can be divided into four chemical groupings: (1) the morphine derivatives (levorphanol, butorphanol), (2) the diphenylheptane derivatives (methadone, propoxyphene), (3) the benzomorphan derivatives (pentazocine, phenazocine) and (3) the phenylpiperidine derivatives (pethidine, alfentanil, fentanyl, sufentanil and (4) remifentanil) (Table 1) (Pathan &Williams, 2012).
There have been attempts made over the decade to produce compunds that are not only effective painkillers but also have lower dependance liablility. Even though trying to separate their analgesic properties from their dependance liability properities have not been succuessful, the search for new compunds led to the classification of opioids according to their effect at opioid receptors sites.
Opioids can therefore be considered as (1) agonists, (2) partial agonists and (3) antagonists. Agonists interact with a receptor to produce a maximal response from that receptor (ex. analgesia following morphine administration). An, antagonists bind to receptors but does not stimulate a response instead prevents the agonist from binding to that receptor (i.e. naloxone). Partial agonists such as buprenorphine bind to receptors but will elicit only a partial functional response (Pathan & Williams, 2012).
Opioid Receptors
Opioids can also be categorized according to the type of opioid receptor at which they produce their effects. In 1973 , a graduate student, Candice Pert, discovered that morphine attached to specific areas of the brain called the morphine receptors. The research to find molecules that would endogenously stimulate that receptors led to the discovery of endogenouse morpheines or endorphines and opioid receptor types (Hart et al., 2012).
There are considered to be three opioid receptors which were originally named "mu (after morphine, its most commonly recognized exogenous ligand), delta (after vas deferens, the tissue within which it was first isolated) and kappa (after the first ligand to act at this receptor, ketocyclazocine)" (Pathan & Williams, 2012).
Only receptors that effect brains pleasure pathways will be mention in the next section
Mu - Mu receptors are found primarily in the brain stem and medial thalamus and are responsible for supraspinal analgesia, respiratory depression, euphoria, sedation and physical dependence. Subtype mu1 is related specifically to analgesia, euphoria, and serenity (Hart et al., 2012).
Kappa - Kappa agonist are found in the lymbic and other diencephalic areas, brain stem, and spinal cord, and are responsible for spinal analgesia, sedation, dysphoria ( unhappiness or unease) and dependence among other things (Hart et al., 2012).
Moreover, opioids and endogenous opioids activate presynaptic receptors on GABA neurons which inhibits the release of GABA in the ventral tegmental area. This inhibition of GABA allows dopaminergic neurons to fire more vigorously, and this extra dopemine in the nuclears accumbens results in intense feelings of pleasure (Hart et al., 2012).
Classifications
Opioids can be classified according to their mode of synthesis into alkaloids: semi-synthetic and synthetic compounds. Raw opium contains morphine and smaller amounts of codeine and simple chemical manipulations of these basic opiate alkaloids will yield a range of semi-synthetic opioids.
As noted in Drugs Behaviour and Society (Hart, Ksir, Hebb,Gilbert & Black, 2012) adding two acetyl groups to the morphine molecule results in Heroin. Heroin to readily penetrates the blood brain barrier making it two to three times more potent than morphine.
During the 20th century a number of synthetic opioids were also produced. These synthetic compounds can be divided into four chemical groupings: (1) the morphine derivatives (levorphanol, butorphanol), (2) the diphenylheptane derivatives (methadone, propoxyphene), (3) the benzomorphan derivatives (pentazocine, phenazocine) and (3) the phenylpiperidine derivatives (pethidine, alfentanil, fentanyl, sufentanil and (4) remifentanil) (Table 1) (Pathan &Williams, 2012).
There have been attempts made over the decade to produce compunds that are not only effective painkillers but also have lower dependance liablility. Even though trying to separate their analgesic properties from their dependance liability properities have not been succuessful, the search for new compunds led to the classification of opioids according to their effect at opioid receptors sites.
Opioids can therefore be considered as (1) agonists, (2) partial agonists and (3) antagonists. Agonists interact with a receptor to produce a maximal response from that receptor (ex. analgesia following morphine administration). An, antagonists bind to receptors but does not stimulate a response instead prevents the agonist from binding to that receptor (i.e. naloxone). Partial agonists such as buprenorphine bind to receptors but will elicit only a partial functional response (Pathan & Williams, 2012).
Opioid Receptors
Opioids can also be categorized according to the type of opioid receptor at which they produce their effects. In 1973 , a graduate student, Candice Pert, discovered that morphine attached to specific areas of the brain called the morphine receptors. The research to find molecules that would endogenously stimulate that receptors led to the discovery of endogenouse morpheines or endorphines and opioid receptor types (Hart et al., 2012).
There are considered to be three opioid receptors which were originally named "mu (after morphine, its most commonly recognized exogenous ligand), delta (after vas deferens, the tissue within which it was first isolated) and kappa (after the first ligand to act at this receptor, ketocyclazocine)" (Pathan & Williams, 2012).
Only receptors that effect brains pleasure pathways will be mention in the next section
Mu - Mu receptors are found primarily in the brain stem and medial thalamus and are responsible for supraspinal analgesia, respiratory depression, euphoria, sedation and physical dependence. Subtype mu1 is related specifically to analgesia, euphoria, and serenity (Hart et al., 2012).
Kappa - Kappa agonist are found in the lymbic and other diencephalic areas, brain stem, and spinal cord, and are responsible for spinal analgesia, sedation, dysphoria ( unhappiness or unease) and dependence among other things (Hart et al., 2012).
Moreover, opioids and endogenous opioids activate presynaptic receptors on GABA neurons which inhibits the release of GABA in the ventral tegmental area. This inhibition of GABA allows dopaminergic neurons to fire more vigorously, and this extra dopemine in the nuclears accumbens results in intense feelings of pleasure (Hart et al., 2012).