Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver.

Background: NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.

Methods: A dilutional pharmacokinetic system was used for in vitro experiments.

Occipital nerve block for headaches: a narrative review.

The occipital nerve block involves the injection of a local anesthetic and possibly a corticosteroid near the occipital nerves at the base of the skull and aims at providing relief from chronic headaches by temporarily numbing or reducing inflammation around the occipital nerves. It has proven to be efficacious in treating chronic headaches, especially those that are refractory to medication; it is both diagnostic and therapeutic with symptom abatement from weeks to months. Occipital nerve blocks can be utilized alone or with standard-of-care therapy for various other headache conditions, such as cluster headaches, episodic headaches or chronic migraines.

Mechanistic Insights into the Adenosine A1 Receptor's Positive Allosteric Modulation for Non-Opioid Analgesics.

The adenosine A1 receptor (AR) is a promising target for pain treatment. However, the development of therapeutic agonists is hampered by adverse effects, mainly including sedation, bradycardia, hypotension, or respiratory depression. Recently discovered molecules able to overcome this impediment are the positive allosteric modulator MIPS521 and the A1R-selective agonist BnOCPA, which are both potent and powerful analgesics with fewer side effects.

Safety, tolerability, pharmacokinetics, and antimalarial activity of MMV533: a phase 1a first-in-human, randomised, ascending dose and food effect study, and a phase 1b Plasmodium falciparum volunteer infection study.

Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.

Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).