Viloxazine is a selective norepinephrine reuptake inhibitor that has a long history of clinical use in Europe as an antidepressant. An immediate-release formulation was approved for the treatment of depression in the UK in 1974, and was subsequently marketed there and in several European countries for 30 years with no major safety concerns. In April of 2021, the United States Food and Drug Administration (FDA) approved the use of viloxazine (QELBREE), developed by Supernus Pharmaceuticals, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult patients. Approval was based on positive results from a series of short-term phase III clinical trials in which viloxazine improved the severity of ADHD symptoms in children and adolescents with diagnosed ADHD. Viloxazine is available as extended-release capsules for once-daily oral administration.

Samidorphan, which was developed by Alkermes, is an opioid receptor antagonist that has been co-formulated with olanzapine into a single-dose oral tablet to mitigate the risk of weight gain while providing the therapeutic effect of olanzapine. In June 2021, the Food and Drug Administration (FDA) approved Lybalvi (olanzapine/samidorphan) for indications including treatment of adults with schizophrenia and/or bipolar I disorder (acute manic episodes or acute episodes with mixed features).

Difelikefalin (Korsuva™) is a synthetic peptide agonist of the kappa opioid receptor being developed by Cara Therapeutics for the treatment of pruritus. In August 2021, intravenous difelikefalin was approved in the USA for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD) in adults undergoing haemodialysis. Difelikefalin selectively acts on kappa opioid receptors in peripheral tissues, which contribute to pruritis and nociception. The activation of opioid receptors in peripheral neurons and keratinocytes reduces afferent (sensory) impulses towards the central nervous system, decreasing pain signals. Activating kappa opioid receptors on immune cells, including monocytes and T lymphocytes, decreases the release of pro-inflammatory chemicals such as prostaglandins.

Berotralstat (ORLADEYO™; BCX7353) is an orally administered kallikrein inhibitor, which has been developed by BioCryst Pharmaceuticals for hereditary angioedema (HAE). The inhibition of kallikrein by berotralstat decreases the production of bradykinin, which prevents the localised tissue oedema that occurs during attacks of HAE. Berotralstat has been approved in the USA, and subsequently in Japan, for prophylaxis to prevent attacks of HAE in adults and paediatric patients aged 12 years or older.

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

Berotralstat (ORLADEYO™; BCX7353) is an orally administered kallikrein inhibitor, which has been developed by BioCryst Pharmaceuticals for hereditary angioedema (HAE). The inhibition of kallikrein by berotralstat decreases the production of bradykinin, which prevents the localised tissue oedema that occurs during attacks of HAE. Berotralstat has been approved in the USA, and subsequently in Japan, for prophylaxis to prevent attacks of HAE in adults and paediatric patients aged 12 years or older.

Remimazolam is an intravenous benzodiazepine sedative-hypnotic with rapid onset and offset of action. This compound undergoes organ-independent metabolism to an inactive metabolite. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation and anesthesia. Phase I and II clinical trials have shown that remimazolam is safe and effective when used for procedural sedation. Phase III clinical trials have been completed investigating efficacy and safety in patients undergoing bronchoscopy and colonoscopy. The developer of this drug has suggested that intensive care unit sedation (beyond 24 hours) could be another possible indication for further development, since it is unlikely that prolonged infusions or higher doses of remimazolam would result in accumulation and extended effect.

Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.

Osilodrostat (INN, USAN) (developmental code name LCI-699) is an orally active, non-steroidal corticosteroid biosynthesis inhibitor which is under development by Novartis for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion (a specific subtype of Cushing's syndrome). Osilodrostat specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β-hydroxylase (CYP11B1). Osilodrostat decreases plasma and urinary aldosterone levels and rapidly corrects hypokalemia, in patients with primary aldosteronism and hypertension. At doses ≥1 mg o.d. Osilodrostat markedly increases 11-deoxycortisol plasma levels and blunts ACTH-stimulated cortisol release in ≈20% of patients, consistent with the inhibition of CYP11B1. In patients with resistant hypertension, Osilodrostat produces a non-significant reduction in blood pressure, possibly due to the increase in 11-deoxycortisol levels and the stimulation of the hypothalamic-pituitary-adrenal feedback axis. Because of the lack of selectivity, poor antihypertensive effect, and short half-life, the development of Osilodrostat as antihypertensive was halted. As of 2017, Osilodrostat is in phase III and phase II clinical trials for the treatment of pituitary ACTH hypersecretion and Cushing's syndrome, respectively.