Mechanism of action of rituximab

The CD20 antigen is strongly and stably expressed on cells of the B-cell lineage, but not on stem cells, and is thus an ideal target antigen for antibody therapy of B-cell malignancies. Rituximab is a human-mouse chimeric monoclonal antibody to the CD20 antigen that kills B-cells by a number of different effector mechanisms. The human IgG component of the antibody is able to bind human complement and also interact with effector cells to kill cells by antibody-dependent cell-mediated cytotoxicity. Some investigators have also shown direct effects of the antibody on human tumor cell lines expressing CD20. These effects include inhibition of proliferation, induction of apoptosis and increased sensitivity to chemotherapeutic agents, although the extent to which each of these mechanisms may contribute to the anti-tumor action of rituximab remains to be determined. Rituximab thus acts by additional mechanisms compared to conventional chemotherapeutic agents. The chimeric nature of the antibody results in minimal immunogenicity and allows repeat use. The antibody may be combined with conventional chemotherapy, with potential for increased efficacy with minimal added toxicity.     

Mechanism of action of guanethidine

The early hypotensive action of intravenous guanethidine in rabbits, rats and cats anaesthetized with urethane is reversed after pretreatment with iproniazid. The fall in blood pressure following injection of guanethidine in rabbits is reduced after previous administration of reserpine. Reserpine, like adrenalectomy and splenectomy, suppresses the early pressor effect of guanethidine in cats anaesthetized with chloralose. Guanethidine inhibits the action of tyramine and nicotine, but potentiates the effect of noradrenaline on isolated rabbit atria. Guanethidine is also a weak inhibitor of monoamine oxidase activity. The results are discussed and compared with those shown by reserpine. It is concluded that the early effects of guanethidine are mainly due to the release of endogenous catechol amines.     

Mechanism of action of memantine

Memantine is a clinically useful drug in many neurological disorders, including Alzheimer's disease. The principal mechanism of action of memantine is believed to be the blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors--a glutamate receptor subfamily broadly involved in brain function. Surprisingly, other drugs that block NMDA receptor channels, such as ketamine, exhibit serious deleterious effects. The unusual therapeutic utility of memantine probably results from inhibitory mechanisms shared with ketamine, combined with actions specific to memantine. These potentially important differences between memantine and ketamine include effects on gating of blocked channels and binding of memantine to two sites on NMDA receptors. Because modulation of NMDA receptor activity can increase or decrease excitability of neuronal circuits, subtle differences in the mechanisms of action of NMDA receptor antagonists can strongly impact on their clinical effects.     

Mechanism of action of antidepressants

A wide range of effective drugs is available for the treatment of major depression. The discovery of these agents has not always been the result of rational drug design. Tricyclic antidepressants formed the mainstay of treatment until the 1990s, and selective serotonin reuptake inhibitors (SSRIs) have dominated treatment over the last decade. However, the poor tolerability associated with tricyclic antidepressants and concerns about the efficacy of SSRIs has led to the search for alternative agents. Attention has focused on those drugs that affect norepinephrine and/or serotonin systems, with the recent introduction of a number of agents, including venlafaxine, milnacipran, nefazodone, mirtazapine, and reboxetine. Venlafaxine, which is the first in a new class of drugs known as serotonin and norepinephrine reuptake inhibitors, may be associated with an earlier onset of action and higher remission rates than SSRIs. It is hoped that the development of drugs with multiple sites of action will translate into improved clinical efficacy in the treatment of depression.     

Mechanism of cardiovascular action of trapidil

In anaesthetized, open-chest dogs N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-alpha]pyrimidine-7-amine (trapidil) in doses of 0.3--3 mg/kg i.v. produced increases in coronary sinus outflow and heart rate and decreases in systemic blood pressure and coronary resistance in a dose-dependent manner. Trapidil produced an increase in myocardial oxygen consumption but virtually no change in coronary arteriovenous oxygen difference. At 1.8 mg/kg i.v. of the drug coronary resistance fell to half of the pre-drug value and coronary sinus outflow almost doubled, and so did myocardial oxygen consumption. In isolated, blood-perfused dog heart preparations, trapidil produced coronary vasodilator and positive inotropic and chronotropic effects. Theophylline produced similar effects. Trapidil was a more positive inotropic than positive chronotropic agent, and so was theophylline but to a lesser degree than trapidil. In producing vasodilator and positive inotropic effects trapidil was about 3 times more effective than theophylline. Trapidil and theophylline inhibited the cyclic AMP phosphodiesterase (PDE) activity in crude extracts prepared from the dog ventricular muscle. In this respect trapidil was nearly 3 times more potent than theophylline. It is suggested that PDE inhibition would be a fundamental mechanism of action of trapidil.     

Mechanism of action of substance P

Summary Synthetic substance P (SP) raises glycine levels both in the brain and in the spinal cord. The synthetic polypeptide, as well as the single amino acid, abolishes motor hyperactivity induced by ,-iminodipropionitrile in mice. The amino acid is effective event at very low intrinsic glycine levels, a condition where the polypeptide fails to act. It is suggested that SP action against exaggerated motories is based on its increasing of spinal glycine which, in turn, inhibits the motor neurones.     

Mechanism of action of hydroxycoumarin derivatives

Experimental and clinical studies have demonstrated the effects of hydroxycoumarin derivatives (pelentan) on the composition and correlation of phospholipids (PL) in red cell biomembranes. PL such as cardiolipin, cholesterol and its esters phosphatidylethanolamine, and phosphatidylcholine experienced the greatest changes. The changes in the composition of biomembrane PL were accompanied by an increase in the total cholesterol content in red cell biomembranes and by an increase in the total and free non-esterified fatty acids in blood plasma (P less than 0.05). At the same time the changes were discovered in the activity of transketolase and glucose-6-phosphate dehydrogenase limiting the pentosephosphate shunt.