Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Aug 2014
ReviewNew investigational drugs for the treatment of neuropathic pain.
Neuropathic pain (NP) is a chronic condition that arises from a lesion or dysfunction of the somatosensory nervous system. However, there are several new targets and novel technologies in the pipeline to address this unmet medical need. ⋯ There is a real hope that new drugs for NP may be available soon. This hope is based on advancing methods of genomics, developing new targets and more efficient drug screening. Some forms of direct influence on voltage-gated ion channels have a place in the treatment of NP, while the development of entirely novel Ang II AT₂ receptor antagonists or NGF inhibitors may be available for many chronic pain sufferers in the foreseeable future.
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Expert Opin Investig Drugs · Aug 2014
ReviewCannabinoids in pain management: CB1, CB2 and non-classic receptor ligands.
Commercially available cannabinoids are subject to psychotomimetic and addiction (cannabinomimetic) adverse effects largely through activation of the cannabinoid 1 receptor (CB1r). The available commercial cannabinoids have a narrow therapeutic index. Recently developed peripherally restricted cannabinoids, regionally administered cannabinoids, bifunctional cannabinoid ligands and cannabinoid enzyme inhibitors, endocannabinoids, which do not interact with classic cannabinoid receptors (CB1r and CB2r), cannabinoid receptor antagonists and selective CB1r agonists hold promise as analgesics. ⋯ Regional and peripherally restricted cannabinoids will reduce cannabinomimetic side effects. Spinal cannabinoids may increase the therapeutic index by limiting the dose necessary for response and minimize drugs exposure to supraspinal sites where cannabinomimetic side effects originate. Cannabinoid bifunctional ligands should be further explored. The combination of a CB2r agonist with a transient receptor potential vanilloid (TRPV-1) antagonist may improve the therapeutic index of the CB2r agonist. Enzyme inhibitors plus TRPV-1 blockers should be further explored. The development of analgesic tolerance with enzyme inhibitors and the pronociceptive effects of prostamides limit the benefits to cannabinoid hydrolyzing enzyme inhibitors. Most clinically productive development of cannabinoids over the next 5 years will be in the area of selective CB2r agonists. These agents will be tested in various inflammatory, osteoarthritis and neuropathic pains.
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Expert Opin Investig Drugs · Jul 2014
ReviewDevelopments in treatments for amyotrophic lateral sclerosis via intracerebroventricular or intrathecal delivery.
Amyotrophic lateral scleroses (ALS) are neurodegenerative disorders primarily affecting the motor system. These incurable disorders are relentlessly progressive and typically limit survival to 2 - 5 years after disease onset. An improved knowledge about disease-causing genes, disease proteins and pathways has revealed considerable heterogeneity in ALS. Novel targeted therapies are being developed, but getting these beyond the BBB remains a challenge. ⋯ Lack of BBB permeability should not hold back the development of promising treatments for ALS, as the available evidence suggest that direct intrathecal or intracerebroventricular administration of drug is a feasible delivery route in patients with ALS.
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Expert Opin Investig Drugs · Jul 2014
ReviewEmerging therapeutic interventions for idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating and relentlessly progressive lung disorder. Previously, it was thought to be a chronic inflammatory disease; however, it is now considered to be an epithelial-fibroblastic disease. In accordance with this paradigm change, efforts toward the development of novel therapeutic targets for IPF have acquired a new direction. Currently available therapies are largely ineffective in reversing the lung damage, and lung transplantation is the only effective treatment for end-stage disease. Limitations in advancement of IPF therapeutics are due to a poor understanding of its pathogenesis, unavailability of reliable animal models and slow disease progression. Recent research on IPF has resulted in the identification of a plethora of novel targets that are in various stages of development and offers hope that in the near future that there will be better therapeutic options available for the treatment of IPF. ⋯ Targeting one fibrotic signaling pathway at a time may not have any significant effect on the control of IPF. It is therefore recommended that future IPF management focuses on targeting multiple pro-fibrotic pathways associated with its complex pathogenesis.
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Expert Opin Investig Drugs · Jul 2014
ReviewSerelaxin : a potential new drug for the treatment of acute heart failure.
The incidence and mortality related to acute heart failure (AHF) have increased in the recent decades despite clinical trials of multiple agents and considerable progress in cardiovascular disease overall. ⋯ Recent clinical trials of serelaxin (Pre-RELAX-AHF; RELAX-AHF) have provided a new hope in AHF. They have demonstrated significant serelaxin-related improvement in heart failure symptoms, length of hospital stay as well as mortality reduction in AHF patients. These findings were in the context of early administration in the course of AHF presentation in patients with normal or high blood pressures, thus highlighting the drug's strengths based on its molecular mechanisms of action. Overall, serelaxin is a promising therapy, and further studies aimed at reproducibility of prior results, safety and hemodynamic effects of serelaxin, as well as investigation of the molecular reasons for such effects are currently under way.