Terbutaline is a relatively selective beta2-adrenergic bronchodilator that has little or no effect on alpha-adrenergic receptors. The drug has exerts a preferential effect on beta2-adrenergic receptors but stimulates beta-adrenergic receptors less selectively than relatively selective beta2-agonists. Terbutaline appears to have a greater stimulating effect on beta-receptors of the bronchial, vascular, and uterine smooth muscles (beta2 receptors) than on the beta-receptors of the heart (beta1 receptors). This drug relaxes smooth muscle and inhibits uterine contractions, but may also cause some cardiostimulatory effects and CNS stimulation. The pharmacologic effects of terbutaline are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Terbutaline is used for the prevention and reversal of bronchospasm in patients 12 years of age and older with reversible, obstructive airway disease, as well as symptomatic management of reversible bronchospasm associated with bronchitis and emphysema. Also used acute IV and sub-Q therapy in selected women to inhibit uterine contractions in preterm labor (tocolysis) and prolong gestation when beneficial.

Methoxsalen — also called xanthotoxin, marketed under the trade names Oxsoralen, Deltasoralen, Meladinine — is a drug used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to UVA light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10 mg tablets, which are taken in the amount of 30 mg 75 minutes before a PUVA (psoralen + UVA) light treatment. Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically. The exact mechanism of action of methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional adducts (crosslinking of psoralen to both strands of DNA) Reactions with proteins have also been described. Methoxsalen acts as a photosensitizer. Administration of the drug and subsequent exposure to UVA can lead to cell injury. Orally administered methoxsalen reaches the skin via the blood and UVA penetrates well into the skin. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. The most obvious manifestation of this reaction is delayed erythema, which may not begin for several hours and peaks at 48–72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum. The mechanisms of therapy are not known. In the treatment of vitiligo, it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and to repopulate the epidermis. In the treatment of psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also be playing some role. Psoriasis is a hyperproliferative disorder and other agents known to be therapeutic for psoriasis are known to inhibit DNA synthesis. The most commonly reported side effect of methoxsalen alone is nausea, which occurs with approximately 10% of all patients. This effect may be minimized or avoided by instructing the patient to take methoxsalen with milk or food, or to divide the dose into two portions, taken approximately one-half hour apart. Other effects include nervousness, insomnia, and psychological depression.

Morphine is one of the most important and widely used opioid for the treatment of chronic and acute pain: the very wide interindividual variability in the patients’ response to the drug may have genetic derivations. Sulphate salt of morphine sold under the many brand names, one of them, DURAMORPH, which is indicated for the management of pain severe enough to require use of an opioid analgesic by intravenous administration, and for which alternative treatments are not expected to be adequate. In addition for the epidural or intrathecal management of pain without attendant loss of motor, sensory, or sympathetic function. Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Morphine has a high potential for addiction and abuse. Common side effects include drowsiness, vomiting, and constipation. Caution is advised when used during pregnancy or breast-feeding, as morphine will affect the baby.

Implitapide is a microsomal triglyceride transfer protein (MTP) inhibitor with antihyperlipidemic activity. Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of both chylomicron in the intestine and very low-density lipoprotein in the liver. In an animal model, inhibition of MTP by implitapide reduced both total cholesterol and triglyceride levels and suppressed progression of atherosclerotic lesions in apolipoprotein E knockout mice fed a Western-type diet.

Ibuterol, a prodrug that is rapidly hydrolyzed to form a drug, terbutaline. Terbutaline, a beta-2 adrenergic agent used to treat asthma.

Ammonium trichlorotellurate (AS-101) is a synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immunostimulatory and anti-hair loss properties. Ammonium trichlorotellurate induces production of colony stimulating factor (CSF), interleukin-2 (IL-2), and IL-2 receptors by increasing the calcium ion influx through the cell membrane and subsequently exerts its immunostimulatory effects through the CSF-mediated increase in macrophage/granulocytes. This agent is also a potent inducer of interferon and a spectrum of cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF). In animal studies, ammonium trichlorotellurate exerts its anti-hair loss effect by inducing anagen and obstructing spontaneous catagen via promoting follicular keratinocyte proliferation and interfering with terminal differentiation, respectively. AS-101 suppresses production of HIV-1. It inhibited reverse transcriptase activity and replication of human immunodeficiency virus type 1. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 uM. Intravenous AS-101 was in trials in patients with HIV infections. AS-101, a small-molecule integrin αvβ3 and VLA-4 inhibitor is being developed by BioMAS in Israel for the treatment of genital warts, age-related macular degeneration and fertility preservation. Phase II clinical trials are ongoing. The drug was also undergoing phase II development in acute myeloid leukaemia, atopic dermatitis, chemotherapy-induced damage, myelodysplastic syndromes, thrombocytopenia, alopecia, psoriasis. However, development for these indications was discontinued.

PF-03463275 is the novel azabicyclic glycine transporter 1 (GlyT1) inhibitor. Ketamine induced hallucinatory-like behaviors that were not reversed by PF-3463275. In contrast, all doses of PF-3463275 alleviated the deficit in spatial working memory induced by ketamine. PF-03463275 causes changes in electroretinogram (ERG) responses in albino rats. There was dose-dependent reduction in the amplitude of the rat ERG oscillatory potentials (OPs) following single subcutaneous administrations of the PF-03463275. Furthermore, the amplitude of OPs was negatively correlated to the concentration of PF-03463275 in the vitreous humor collected from rats immediately following ERG recordings. A slight increase in the amplitude and latency of the a-wave component of the ERG with PF-03463275 treatment was observed. Since the ERG changes occur in our rodent model with PF-03463275 at exposures comparable with those associated with visual disturbance in the clinic, it was proposed that the visual adverse effects reported in healthy volunteers treated with selective GlyT1 inhibitors may represent a retinal class effect. The dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in schizophrenia patients. PF-03463275 had been in phase II clinical trial for the treatment of schizophrenia. However, this development was discontinued.

Growth hormone releasing hexapeptide (GHRP-6) is a synthetic met-enkephalin analog that induces the release of growth hormone in vivo through binding of the ghrelin receptor. GHRP-6 increases proliferation in astrocytes through a mechanism that involves PI3K/Akt signaling. GHRP-6 also inhibits development of restraint stress-induced gastric lesions and reverses ovariectomy-induced effects on serum glucose and insulin levels. Additionally, GHRP-6 decreases locomotor activity and increases food intake in vivo. Essentially a synthetic version of ghrelin analogue, GHRP-6 (like GHRP-2) stimulates the release of an endogenous growth hormone (GH) within the somatotropes of the anterior pituitary in the animal and human body. Specifically, GHRP-6 will increase the number of somatotropes in a GH pulse by limiting the amount of somatostatin present, while standard GHRH increases the amplitude at which the pituitary cells pulse. Unlike ghrelin, GHRP-6 is not specifically used to increase appetite, but it may have secondary actions that impact hypothalamic neurons. These effects last for approximately an hour after the initial application, which mimics the natural application of GH, and consists of an eight hour circulation period. In studies GHRP-6 has shown biological actions similar to the naturally occurring hunger stimulating peptide ghrelin. Its main use is to promote food intake by stimulating hunger and aid in energy metabolism. It can be used in the treatment of GH deficiency as well as cachexia, eating disorders and obesity. GHRP-6 is a synthetic met-enkephalin (a naturally occurring opioid growth factor) analog. GHRP-6 contains D-amino acids that are entirely synthetic, lacks opioid activity, and shares no sequence relation with GHRH. It has also been shown that GHRP-6 can lead to re-stimulation of the natural production of HGH. Studies have shown that GHRP-6 increases the secretion of IGF-1 (InsulinLike Growth Factor 1) by the liver, which is speculated to be a required component in the anabolic mechanisms leading to the action of HGH. It also appears that GHRP-6 has positive implications for the central nervous system, as ghrelin is known to protect neurons.