Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Sep 2007
Review Comparative StudyThe use of herbal medicines in early drug development for the treatment of HIV infections and AIDS.
This review systematically assesses the beneficial and harmful effects of herbal medicines in people with HIV infection and AIDS. Based on a Cochrane review and updated searches, the author identifies the available evidence on herbal medicines compared with placebo or antiretroviral drugs in patients with HIV infection, HIV-related disease or AIDS. ⋯ Combined treatment of Chinese herbal medicine, SH and antiretroviral agents showed increased antiviral benefit compared with antiretrovirals alone. These findings suggest beneficial effects from some of the tested herbs but more evidence from larger studies are needed to support this evidence in the future.
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Expert Opin Investig Drugs · Sep 2007
ReviewNew therapeutic perspectives with clevidipine: an ultra-short-acting intravenous Ca2+ channel blocker.
Intravenous antihypertensive agents are used in clinical situations in which the immediate, precise control of blood pressure is a clinical necessity. Clevidipine is a new, vascular-selective, dihyrdopyridine Ca(2+) channel blocker, which exerts its hemodynamic effects through selective arterial vasodilation without effects on the venous circulation. Because it is a potent coronary vasodilator, reduction in mean arterial pressure does not impair coronary perfusion. ⋯ In clinical trials performed in patients undergoing cardiac surgery, clevidipine proved superior to nitroprusside and nitroglycerin in maintaining blood pressure within predetermined ranges during the perioperative period. Its safety profile is comparable to nicardipine and nitroglycerin and, in one study, was associated with reduced 30-day mortality compared with nitroprusside. Clevidipine constitutes a useful addition to available intravenous agents and could prove particularly valuable in circumstances that require the ability to rapidly terminate the blood pressure-lowering effects of administered agents.
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Expert Opin Investig Drugs · Sep 2007
ReviewTriple uptake inhibitors: therapeutic potential in depression and beyond.
Drugs that interfere with the uptake and/or metabolism of biogenic amines have been used to treat depression for > 4 decades. Early medications such as tricyclic antidepressants and monoamine oxidase inhibitors are effective but possess many side effects that limit their usefulness. Selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) are the results of rational design to find drugs that are as effective as the tricyclic antidepressants, but with more selectivity towards a single monoamine transporter. ⋯ An important recent development has been the emergence of the triple uptake inhibitors (SSRI/SNRI/selective dopamine reuptake inhibitor), which inhibit the uptake of all three neurotransmitters that are most closely linked to depression: serotonin, noradrenaline and dopamine. Preclinical studies and clinical trials indicate that a drug inhibiting the uptake of all three of these neurotransmitters could produce a more rapid onset of action and possess greater efficacy than traditional antidepressants. This review discusses the evolution of biogenic amine-based therapies, the emerging strategies involved in the design and synthesis of novel triple uptake inhibitors as antidepressants and the therapeutic potential of triple uptake inhibitors.
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Expert Opin Investig Drugs · Aug 2007
ReviewOxytrex: an oxycodone and ultra-low-dose naltrexone formulation.
Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. ⋯ The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.
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There is convincing evidence that angiotensin II, through activation of the angiotensin II type 1 (AT1) receptor, is involved in the atherosclerotic process. Similarly, angiotensin receptor blockers decrease vascular inflammation, hypertrophy and thrombosis, which are the key components of the progression of atherosclerosis. In addition, in several animal models, angiotensin receptor blockade was able to inhibit atherosclerosis. ⋯ Contradictory results have been found on the reduction of the risk on myocardial infarctions and in-stent restenosis, although there is solid evidence for cerebroprotective effects of these receptor blockers. These differences may be related to the role of the AT2 receptor. This review discusses the role of angiotensin II and angiotensin receptor blockers in the atherosclerotic process and its translation into clinical practice.