Meperidine is a narcotic analgesic opioid that is used for moderate to severe pain. It is less effetive than Morphine, but also has shorter side-effects. Mepereidine is effective locally or in the central nervous system in the brain and spinal cord. It can ross the blood-brain barrier to access the brain. It is regularly injected, but sometimes can be taken orally which has a 50-60% bioavailability because of first pass metabolism in the liver. In the nervous system meperidine binds to the kappa-type opioid receptor. The Kappa-opioid receptor is coupled with G-protein receptors. Binding of meperidine stimulates the exchange of GTP for GDP on the G-protein complex. The G-protein system inhibits adenylate cyclase which prevents ATP from being synthesized into cAMP which causes a decrease in intracellular cAMP. The activated G-proteins also close N-type voltage-operated calcium channels which prevents calcium from entering the neuron, and it opens calcium-dependent inwardly rectifying potassium channels which causes sodium to leave the neuron. This results in hyperpolarization and reduced neuronal excitability. Subsequently, this leads to the release of nociceptive neurotransmitters such as GABA, substance P, dopamine, acetylcholine, and noradrenaline. Less GABA leads to disinhibition of dopamine cell firing in the spinal cord and brain pain transmission neurons as well as the pleasure center of the brain. Less substance P, acetylcholine, and noradrenaline directly prevents firing of nociceptors as they bind and activate receptors that cause firing in nociceptors. Both these neurotransmitters and GABA lead to analgesia. Dopamine while normally not present in the pain pathway to cause pain, but has been shown to be involvedin chronic pain, and meperidine can stop that pain as well. Meperidine also has side-effects caused by the activation of opioid receptors in muscle signalling. Opioid receptors prevent the release of acetylcholine which is the neurotransmitter used on smooth muscles. This therefore prevents contraction of those smooth muscles which can lead to constipation and depression of the cough reflex.

Meperidine opioid agonist Pathway References