Pharmacology Opioid

1 pharmacology

1.1 functional selectivity
1.2 opioid comparison
1.3 binding profiles

pharmacology

opioids bind specific opioid receptors in nervous system , other tissues. there 3 principal classes of opioid receptors, μ, κ, δ (mu, kappa, , delta), although seventeen have been reported, , include ε, ι, λ, , ζ (epsilon, iota, lambda , zeta) receptors. conversely, σ (sigma) receptors no longer considered opioid receptors because activation not reversed opioid inverse-agonist naloxone, not exhibit high-affinity binding classical opioids, , stereoselective dextro-rotatory isomers while other opioid receptors stereo-selective levo-rotatory isomers. in addition, there 3 subtypes of μ-receptor: μ1 , μ2, , newly discovered μ3. receptor of clinical importance opioid-receptor-like receptor 1 (orl1), involved in pain responses having major role in development of tolerance μ-opioid agonists used analgesics. these g-protein coupled receptors acting on gabaergic neurotransmission.

locants of morphine molecule

the pharmacodynamic response opioid depends upon receptor binds, affinity receptor, , whether opioid agonist or antagonist. example, supraspinal analgesic properties of opioid agonist morphine mediated activation of μ1 receptor; respiratory depression , physical dependence μ2 receptor; , sedation , spinal analgesia κ receptor. each group of opioid receptors elicits distinct set of neurological responses, receptor subtypes (such μ1 , μ2 example) providing more [measurably] specific responses. unique each opioid distinct binding affinity various classes of opioid receptors (e.g. μ, κ, , δ opioid receptors activated @ different magnitudes according specific receptor binding affinities of opioid). example, opiate alkaloid morphine exhibits high-affinity binding μ-opioid receptor, while ketazocine exhibits high affinity ĸ receptors. combinatorial mechanism allows such wide class of opioids , molecular designs exist, each own unique effect profile. individual molecular structure responsible different duration of action, whereby metabolic breakdown (such n-dealkylation) responsible opioid metabolism.

inta: selective agonist of kor-dor , kor-mor heteromers. not recruit β-arrestin ii. antinociceptive devoid of aversion, tolerance, , dependence in mice.


functional selectivity

a new strategy of drug development takes receptor signal transduction consideration. strategy strives increase activation of desirable signalling pathways while reducing impact on undesirable pathways. differential strategy has been given several names, including functional selectivity , biased agonism. first opioid intentionally designed biased agonist , placed clinical evaluation drug oliceridine. displays analgesic activity , reduced adverse effects.

opioid comparison

extensive research has been conducted determine equivalence ratios comparing relative potency of opioids. given dose of opioid, equianalgesic table used find equivalent dosage of another. such tables used in opioid rotation practices, , describe opioid comparison morphine, reference opioid. equianalgesic tables typically list drug half-lives, , equianalgesic doses of same drug means of administration, such morphine: oral , intravenous.

binding profiles