Abstract
A combination of basic research observations concerning the interaction of somatostatin (SST) and dopamine (DA) receptors, and clinical reports of enhanced efficacy of combined SST and DA analogue treatment in suppressing GH hypersecretion, lead to the concept of creating chimeric molecules combining structural features of both compound classes.
The resulting SST/DA chimeras retain the ability to interact with receptors of both families and display greatly enhanced potency and efficacy, as compared with that of individual SST or DA receptor agonists.
In vitro studies with pituitary adenoma cells from acromegalic patients have demonstrated that the chimeric molecules have exceptional activity with regard to suppression of GH and prolactin secretion.
Similarly, potent suppression of ACTH secretion from Cushing's-causing corticotroph tumors, and suppression of nonfunctioning pituitary adenoma proliferation has been observed.
The chimeric SST/DA compounds are also quite potent and efficacious in suppressing both GH and IGF1 in vivo when tested in nonhuman primates, with no effect on either insulin secretion or glycemic control.
Initial clinical studies examining acute, subcutaneous administration of the chimeric SST/DA compound, BIM-23A760, revealed both prolonged circulating half-life and extended duration of biological effect.
With chronic administration, however, BIM-23A760 was found to produce a metabolite with dopaminergic activity that gradually accumulates and interferes with the activity of the parent compound.
Consequently, efforts are currently underway to produce a second-generation chimera for treatment of neuroendocrine disease.
See also:
- Official Web Site: The Di Bella Method;
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Oesophageal squamocellular carcinoma: a complete and objective response;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Complete objective response to biological therapy of plurifocal breast carcinoma;
- Neuroblastoma: Complete objective response to biological treatment.