1,721,117 research outputs found
Serotonin-enhancing drugs
No full textThrough its projections to various brain areas, serotonin participates to the control of numerous functions, like sleep, mood regulation, fear and anxiety, aggressiveness, motivation and reward, learning and memory, hunger, sexual activity, circadian rhythm regulation, neuroendocrine regulation, stress response and pain sensitivity. The multiplicity of the effects mediated by serotonin derives from the interaction of this neurotransmitter with a wide variety of membrane receptors localized in both the nervous system (central and peripheral) and peripheral organs. In fact, such receptors were localized also in the heart and other sites of the cardiovascular system, as well as in the gastrointestinal system. Recent genetic and molecular biology studies lead to the identification of at least 15 different serotonin receptor subtypes that ensure enormous variability in the response associated to the serotonergic system. However, despite the elevated number of receptors, serotonin receptor pharmacology is relatively recent, and few are the drugs currently marketed which act at a serotonin receptor level. Hence, the drugs which are better known as serotonergic system modulators are not the agonists or antagonists of the various serotonin receptor subtypes, but the serotonin transporter inhibitors. These are drugs that block neuronal serotonin reuptake, although with different potency and selectivity, and are effective in treating mood, depressive, anxiety, and eating disorders
International Academy for Biomedical and Drug Research Consensus Conference, San Juan, December 8-9, 1996: Novel therapeutic indications of antidepressant drugs: Introduction
No full textPhysiology to functionality: The brain and neurotransmitter activity
No full textThe monoamine hypothesis of depression proposes that the biological basis for depression is a deficiency in the neurotransmitters serotonin or noradrenaline, or both. Over the past 30 years this hypothesis has been refined as more experimental and clinical evidence has emerged. The selective serotonin reuptake inhibitors in particular have made a significant contribution to our understanding of the role of serotonin in depression. Our knowledge of the noradrenergic system is less complete, mainly because, until recently, no equivalent agents were available for this system. With the advent of reboxetine, the first selective noradrenaline reuptake inhibitor, attention is again focusing on the role of noradrenaline in depression. To an extent, the action of the selective inhibitors can be predicted through knowledge of the neuroanatomy of the central and peripheral nervous systems. With regard to depression, the most important pathways are those of the serotonergic and noradrenergic neurones projecting to the prefrontal cortex, from the raphe nucleus and locus coeruleus, respectively. However, increasing the levels of the monoamines in the central nervous system affects many other pathways and a wide range of serotonin and adrenergic receptors, leading to a multiplicity of potential beneficial and adverse events. In addition, the complex intracellular responses are beginning to be examined, again with the aid of the selective antidepressants
Transynaptic mechanisms in the action of antidepressant drugs
No full textAntidepressant drugs act on different neuronal system and pre- and postsynaptic sites. Integrated transynaptic events are considered to be involved in those adaptive changes which seem to be operative after a prolonged administration. The authors explain how these long-term effects, rather than the acute pharmacological actions, are most likely to represent the biochemical mechanism underlying the delayed onset of antidepressant therapeutic efficacy. Among the possible mechanisms responsible for the adaptation of central aminergic neurons, interactions between serotonergic and noradrenergic systems, chemico-physical properties of the membranes and the modulatory actions of hormones and cotransmitters are considered. © 1984
Rationale for the development of noradrenaline reuptake inhibitors
No full textElucidation of the mechanism of action of antidepressants led to the hypothesis that depression is caused by dysfunction in either the noradrenergic or serotonergic neurotransmitter systems. As inconsistencies in studies designed to confirm this hypothesis arose, the consensus on the biological basis of depression is being refined. The need for better tolerated and effective antidepressants has resulted in the development of agents with more specific receptor binding profiles than the tricyclic antidepressants. These newer antidepressants selectively inhibit the reuptake of noradrenaline (selective NARIs), serotonin (SSRIs) or both (SNRIs). They are useful tools for describing changes in neuroreceptors and intracellular events that occur during antidepressant pharmacotherapy. Reboxetine, a selective NARI, down-regulates beta-adrenergic receptors and desensitises noradrenaline-coupled adenylate cyclase. It also affects cAMP- and Ca2+/calmodulin-dependent phosphorylation systems in a different manner to tricyclic antidepressants and SSRIs. This implies that although different classes of antidepressants may affect common central pathways, the ways in which they do this are distinctive. In conclusion, reboxetine, a selective NARI which is well tolerated and effective in the treatment of depression, has provided us with a new insight into the action of antidepressants and thus will help us to refine our theory of the biological basis of depression.Elucidation of the mechanism of action of antidepressants led to the hypothesis that depression is caused by dysfunction in either the noradrenergic or serotonergic neurotransmitter systems. As inconsistencies in studies designed to confirm this hypothesis arose, the consensus on the biological basis of depression is being refined. The need for better tolerated and effective antidepressants has resulted in the development of agents with more specific receptor binding profiles than the tricyclic antidepressants. These newer antidepressants selectively inhibit the reuptake of noradrenaline (selective NARIs), serotonin (SSRIs) or both (SNRIs). They are useful tools for describing changes in neuroreceptors and intracellular events that occur during antidepressant pharmacotherapy. Reboxetine, a selective NARI, down-regulates β-adrenergic receptors and desensitises noradrenaline-coupled adenylate cyclase. It also affects cAMP- and Ca2+/calmodulin-dependent phosphorylation systems in a different manner to tricyclic antidepressants and SSRIs. This implies that although different classes of antidepressants may affect common central pathways, the ways in which they do this are distinctive. In conclusion, reboxetine, a selective NARI which is well tolerated and effective in the treatment of depression, has provided us with a new insight into the action of antidepressants and thus will help us to refine our theory of the biological basis of depression
The septal-hippocampal cholinergic pathway: Role in antagonism of pentobarbital anesthesia and regulation by various afferents
No full textEarlier studies have demonstrated that pentobarbital reduces the turnover rate of acetylcholine (ACh) in hippocampus and that this effect may be mediated via the septal-hippocampal cholinergic pathway. Moreover, the narcosis associated with the administration of pentobarbital may be reversed by intraseptal injection of such chemically diverse compounds as bicuculline, a potent γ-aminobutyric acid antagonist; thyrotropin-releasing hormone, a neuroactive tripeptide; and kainic acid, a rigid analog of glutamate. To determine whether or not these three compounds modulate the metabolism of ACh in hippocampus, they have been injected intraseptally in pentobarbital-pretreated rats and the turnover rate of ACh has been determined by gas chromatography-mass fragmentography. Pentobarbital produces a dose-dependent decrease in the turnover rate of ACh in cortex and hippocampus but not in striatum. The effect appears to be maximum at 30 min and returns to normal within 15 min of recovering the righting reflex. Slow local infusion of either bicuculline or thyrotropin-releasing hormone into the septum reverses the pentobarbital-induced narcosis and antagonizes the pentobarbital-induced decrease in the hippocampal turnover rate of ACh. Administration of kainic acid into the lateral, but not the medial, septum reduces specifically the glutamic acid decarboxylase activity in the ipsilateral septum without altering the choline acetyltransferase activity or the turnover rate of ACh in the hippocampus. Moreover, kainic acid injected into the lateral septum antagonizes the pentobarbital narcosis and reverses the pentobarbital-induced decrease in the ACh turnover rate in the ipsilateral hippocampus, but not in the contralateral hippocampus. It appears that all three compounds antagonize the pentobarbital-induced decrease in hippocampal ACh turnover rate and the pentobarbital narcosis by modulating neurons in the lateral septum, presumably through an action on the GABAergic interneurons
Increased choline availability fails to increase acetylcholine turnover rate in rat brain areas
No full textDifferent adaptive responses by rat striatal dopamine synthetic and receptor mechanisms after repeated treatment with d-amphetamine, methylphenidate and nomifensine
No full textThe effect of repeated administration of d-amphetamine (AMP), methylphenidate (MP) and nomifensine (NOM) on dopamine receptors, striatal adenylate cyclase and tyrosine hydroxylase was studied. No one of the three stimulating drugs changed the receptor number or their affinity to haloperidol specific binding. Adenylate cyclase from rats treated with NOM showed a subsensitivity to the stimulation by dopamine. AMP treatment decreased the activity of striatal tyrosine hydroxylase. MP was ineffective in all the parameters studied. These results show that drugs believed to belong to the same class of stimulants are different in their effect on the CNS adaptive mechanisms
Ontogenetic study of [3H]imipramine binding sites and serotonin uptake system: Indication of possible interdependence
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