Browsing Pathways

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAID) with marked anti-inflammatory and analgesic properties. It is used to treat osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Aceclofenac targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes gastric tolerance compared to the other NSAIDs. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Aceclofenac inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. This drug is administered as an oral tablet.

Acemetacin is highly metabolized and degraded by esterolytic cleavage to form its major and active metabolite indometacin. Indomethacin is a nonsteroidal anti-inflammatory (NSAID) used for the symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants. This drug is not FDA, Canada or EMA approved. It has analgesic, antipyretic, and anti-inflammatory effects. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Indomethacin inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because indomethacin decreases PGE2 in the CNS, it has an antipyretic effect. In clinical trials, acemetacin exhibits better gastric tolerability compared to its active metabolite indometacin.

Acenocoumarol (also known as Nitrowarfarin or Sinthrome) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.

Acepromazine is a phenothiazine tranquilizer that blocks dopamine receptors in the CNS and depresses the reticular-activating system, resulting in sedation. Acepromazine was first used in humans in the 1950s as an antipsychotic agent. It is now rarely used in humans. Acepromazine is frequently used in animals as a sedative and antiemetic. Its principal value is in quietening and calming anxious animals. Acepromazine acts as an antagonist (blocking agent) on different postsynaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapyramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).

Acepromazine is a phenothiazine tranquilizer that blocks dopamine receptors in the CNS and depresses the reticular-activating system, resulting in sedation. Acepromazine was first used in humans in the 1950s as an antipsychotic agent. It is now rarely used in humans. Acepromazine is frequently used in animals as a sedative and antiemetic. Its principal value is in quietening and calming anxious animals. Acepromazine acts as an antagonist (blocking agent) on different postsynaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapyramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).

Aceprometazine is an ethanolamine class H1 antihistamine used to treat insomnia and allergy symptoms such as hay fever and hives. It is also used with pyridoxine in the treatment of nausea and vomiting in pregnancy. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Aceprometazine inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness.