Ghrelin agonist HM01 attenuates chemotherapy-induced neurotoxicity in rodent models.

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is often dose-limiting and impacts life quality and survival of cancer patients. Ghrelin agonists have neuroprotectant effects and may have a role in treating or preventing CIPN. We evaluated the CNS-penetrant ghrelin agonist HM01 in three experimental models of CIPN at doses of 3-30 mg/kg p.o. daily monitoring orexigenic properties, nerve conduction, mechanical allodynia, and intra-epidermal nerve fiber density (IENFD). In a cisplatin-based study, rats were dosed daily for 3 days (0.5 mg/kg i.p.) + HM01. Cisplatin treatment induced mechanical hypersensitivity which was significantly reduced by HM01. In a second study, oxaliplatin was administered to mice (6 mg/kg i.p. 3 times/week for 4 weeks) resulting in significant digital nerve conduction velocity (NCV) deficits and reduction of IENFD. Concurrent HM01 dose dependently prevented the decline in NCV and attenuated the reduction in IENFD. Pharmacokinetic studies showed HM01 accumulation in the dorsal root ganglia and sciatic nerves which reached concentrations > 10 fold that of plasma. In a third model, HM01 was tested in preventive and therapeutic paradigms in a bortezomib-based rat model (0.2 mg/kg i.v., 3 times/week for 8 weeks). In the preventive setting, HM01 blocked bortezomib-induced hyperalgesia and IENFD reduction at all doses tested. In the therapeutic setting, significant effect was observed, but only at the highest dose. Altogether, the robust peripheral nervous system penetration of HM01 and its ability to improve multiple oxaliplatin-, cisplatin-, and bortezomib-induced neurotoxicities suggest that HM01 may be a useful neuroprotective adjuvant for CIPN.

Botanical nomenclature in pharmacovigilance and a recommendation for standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.

Botanical Nomenclature in Pharmacovigilance and a Recommendation for Standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.