Browsing Pathways

Donepezil is an acetylcholinesterase inhibitor also known as Adlarity, Aricept and Namzaric, that is used in the treatment of Alzheimer's Disease and dementia. It is administered orally or transdermally, sometimes in combination with memantine in order to treat moderate to severe dementia. Donepezil selectively inhibits the acetylcholinesterase enzyme, by doing so it is believed to enhance cholinergic transmission to relieve the symptoms of Alzheimer's and dementia. Normally acetylcholinesterase breaks down acetylcholine, this inhibited its enhances cholinergic transmission. Donepezil goes through first-pass metabolism by CYP3A4 and CYP2D6 into metabolites which can be further broken down by dealkylation, hydroxylation, oxidation, hydrolysis and glucuronidation.

Dosulepin is indicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required. Dosulepin displays affinity towards α2-adrenoceptors and to a lesser extent, α1-adrenoceptors. Inhibition of presynaptic α2-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation. Dosulepin binds to 5HT1A and 5HT2A receptors in the cerebral cortex and hippocampus as an antagonist. 5HT1A receptors are autoreceptors that inhibit 5HT release and 5HT2A receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation. Antagonism at 5HT2A receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type 1 (H1) receptors, dosulepin mediates a sedative effect.

Progesterone is a hormone naturally occurring in females. This molecule is essential for endometrial receptivity, embryo implantation, and the successful establishment of pregnancy. It is used as an oral drug as a contraceptive to prevent ovulation and fertilization in certain formulations, as well as a promoter/supporter of pregnancy in other formulations. Pharmaceutical progesterone is made from a plant source as a starting material and is chemically identical to progesterone of human ovarian origin. Progesterone binds its receptor (located both on the membrane and in the cytosol) which activates a signaling pathway resulting in a lower release of GnRH by the hypothalamus. The lower concentration of GnRH results in the transcription of less LH and FSH hormones by the pituitary gland. The overall effect is that the ovaries can't release an egg (no ovulation) and the cervical mucus thicken to be unfavorable for sperm penetration. This drug is administered as an oral tablet/capsule for contraception and as a vaginal gel/insert to maintain the pregnancy.

Progesterone is an endogenous steroid hormone that is commonly produced by the adrenal cortex as well as the gonads, which consist of the ovaries and the testes. Progesterone is also secreted by the ovarian corpus luteum during the first ten weeks of pregnancy, followed by the placenta in the later phase of pregnancy. The conversion of progesterone generation from the corpus luteum to the placenta generally occurs after week ten. The molecule progesterone is a derivative of cholesterol and has numerous functions in the human body, especially within the reproductive system. Molecules of progesterone form from the process of steroidogenesis. Progesterone plays a vital role in the maintenance of the uterus during pregnancy. A progestogen (also called progestagen, gestagen, or gestogen) is a molecule, either natural or synthetic, that shows similar effects as progesterone, binds to the progesterone receptor and acts as an agonist. Progestins are synthetic progestogens. Progesterone utilizes intracellular receptors for their mode of action. Progesterone crosses the membrane of a target cell readily by passive diffusion through the plasma membrane due to its lipophilicity and then binds to and activate progesterone receptors. When unbound, the progesterone receptor exists as a monomer. After binding progesterone, the receptor undergoes a conformational change and becomes a dimer, which increases receptor binding to DNA. Most progestins exert their contraceptive effects by suppressing the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the pituitary gland. This suppression alters the menstrual cycle to suppress ovulation. This progesterone and receptor complex then transports to the nucleus and binds to DNA, specifically near the promoter regions of genes that contain enhancers, containing hormone response elements. This binding of the complex to the promoter can either enhance or repress transcription, which ultimately alters the production of proteins.