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Leslie Iversen

Publications and source records attributed to Leslie Iversen.

7 recordsLinked to original sources
PubMed2006

Neurotransmitter transporters and their impact on the development of psychopharmacology.

The synaptic actions of most neurotransmitters are inactivated by reuptake into the nerve terminals from which they are released, or by uptake into adjacent cells. A family of more than 20 transporter proteins is involved. In addition to the plasma membrane transporters, vesicular transporters in the membranes of neurotransmitter storage vesicles are responsible for maintaining vesicle stores and facilitating exocytotic neurotransmitter release. The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline-selective and serotonin-selective reuptake inhibitors are effective against major depression and a range of other psychiatric illnesses. As the newer drugs are safer in overdose than the first-generation tricyclic antidepressants, their use has greatly expanded. The dopamine transporter (DAT) is a key target for amphetamine and methylphenidate, used in the treatment of attention deficit hyperactivity disorder. Psychostimulant drugs of abuse (amphetamines and cocaine) also target DAT. The amino-acid neurotransmitters are inactivated by other families of neurotransmitter transporters, mainly located on astrocytes and other non-neural cells. Although there are many different transporters involved (four for GABA; two for glycine/D-serine; five for L-glutamate), pharmacology is less well developed in this area. So far, only one new amino-acid transporter-related drug has become available: the GABA uptake inhibitor tiagabine as a novel antiepileptic agent.

Amino Acid Transport Systems↗
PubMed2005

Long-term effects of exposure to cannabis.

The long-term use of cannabis, particularly at high intake levels, is associated with several adverse psychosocial features, including lower educational achievement and, in some instances, psychiatric illness. There is little evidence, however, that long-term cannabis use causes permanent cognitive impairment, nor is there is any clear cause and effect relationship to explain the psychosocial associations. There are some physical health risks, particularly the possibility of damage to the airways in cannabis smokers. Overall, by comparison with other drugs used mainly for 'recreational' purposes, cannabis could be rated to be a relatively safe drug.

Adolescent↗
PubMed2004

GABA pharmacology--what prospects for the future?

Following the recognition of GABA as an inhibitory neurotransmitter, the discovery of high affinity GABA uptake, and the characterisation of GABA receptors great progress has been made in developing GABA pharmacology. Tiagabide, the first marketed GABA uptake inhibitor may be followed by new and more selective uptake inhibitors. Knowledge of the molecular pharmacology of GABA-A receptors, both synaptic and non-synaptic, may lead to improved anti-anxiety/anticonvulsant agents devoid of the sedative and dependence liabilities of earlier compounds and new hypnotics. Gaboxadol (THIP) is an example of a novel hypnotic that acts on GABA-A receptors by a non-benzodiazepine mechanism. Exploiting neurosteroid interactions with GABAergic mechanisms also holds much future promise.

Animals↗
PubMed2003

Cannabis and the brain.

The active compound in herbal cannabis, Delta(9)-tetrahydrocannabinol, exerts all of its known central effects through the CB(1) cannabinoid receptor. Research on cannabinoid mechanisms has been facilitated by the availability of selective antagonists acting at CB(1) receptors and the generation of CB(1) receptor knockout mice. Particularly important classes of neurons that express high levels of CB(1) receptors are GABAergic interneurons in hippocampus, amygdala and cerebral cortex, which also contain the neuropeptides cholecystokinin. Activation of CB(1) receptors leads to inhibition of the release of amino acid and monoamine neurotransmitters. The lipid derivatives anandamide and 2-arachidonylglycerol act as endogenous ligands for CB(1) receptors (endocannabinoids). They may act as retrograde synaptic mediators of the phenomena of depolarization-induced suppression of inhibition or excitation in hippocampus and cerebellum. Central effects of cannabinoids include disruption of psychomotor behaviour, short-term memory impairment, intoxication, stimulation of appetite, antinociceptive actions (particularly against pain of neuropathic origin) and anti-emetic effects. Although there are signs of mild cognitive impairment in chronic cannabis users there is little evidence that such impairments are irreversible, or that they are accompanied by drug-induced neuropathology. A proportion of regular users of cannabis develop tolerance and dependence on the drug. Some studies have linked chronic use of cannabis with an increased risk of psychiatric illness, but there is little evidence for any causal link. The potential medical applications of cannabis in the treatment of painful muscle spasms and other symptoms of multiple sclerosis are currently being tested in clinical trials. Medicines based on drugs that enhance the function of endocannabinoids may offer novel therapeutic approaches in the future.

Animals↗
PubMed2002

Cannabinoids: a real prospect for pain relief?

Research on the therapeutic potential of cannabinoids has grown dramatically over the past few years. Recent advances include evidence that cannabinoid agonists are antihyperalgesic and antiallodynic in models of neuropathic pain. Development of novel cannabinoid agonists and cannabinoid preparations that are antinociceptive has important implications for the therapeutic use of this class of drugs.

Animals↗
PubMed2002

Effects of amidated gastrin and glycine-extended gastrin on cell proliferation and crypt fission in parenterally and orally fed rats.

BACKGROUND/AIMS: It has been suggested that processing variants of gastrin, such as glycine-extended gastrin (G17-Gly), are enterotrophic to the colon. METHODS: Cell proliferation and crypt branching were studied in total parenteral nutrition (TPN) and orally fed rats after infusion of G17-Gly or gastrin-17. RESULTS: Gastrin produced an increase in the weight of the stomach and small intestine and a marked proliferative action on the proximal small intestine, which diminished distally. No proliferative effects of gastrin were seen in the colon. G17-Gly was associated with a small, but significant, increase in colonic weight but had little effect on cell proliferation, except in the gastric fundus. In the distal colon, G17-Gly was associated with a significant decrease in proliferation. Neither agent affected crypt branching in the small intestine or colon, but both proliferation and branching were significantly decreased by TPN. CONCLUSION: Gastrin was trophic to the stomach and the proximal small intestine but not the colon. G17-Gly had only modest proliferative actions on the intestinal epithelium in this study.

Animals↗