Cholecystokinin decreases food intake in rats.

The tachykinin peptide family

The tachykinin peptide family certainly represents one of the largest peptide families described in the animal organism. So far, more than 40 tachykinins have been isolated from invertebrate (insects, worms, and molluscs), protochordate, and vertebrate (skin, gastrointestinal tract, peripheral and central nervous system) tissues. Substance P (SP), first identified by bioassay as early as 1931 but sequenced only in 1971, several years after the elucidation of the structure of eledoisin from molluscan tissues and of physalaemin from amphibian skin, may be considered as a prototype of the tachykinins. Hitherto, as many as 19 tachykinins have been isolated from amphibian integument, and eight additional peptides have been isolated from amphibian gut and brain. Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B. Three main receptor subtypes for the tachykinins have been identified (NK1, NK2, and NK3), but their number is probably destined to increase. It is obvious that the peripheral and central effects of the tachykinins may substantially vary depending on the activation of different receptor subtypes. Matters are further complicated by the frequent capacity of the single tachykinins to bind, although with different affinity, to more receptors. It has been recognized that tachykinins have a variety of effects in physiological and pathological conditions, and there is evidence suggesting intrinsic neuroprotective and neurodegenerative properties of these neuropeptides. This review provides an update on the current body of knowledge regarding tachykinin occurrence and distribution in the animal kingdom, from the lowest invertebrates to man, and the physiological and pharmacological actions of tachykinins outlining the pregnant importance of this large peptide family.

The Tachykinin Peptide Family

Chlorate a potent inhibitor of protein sulfation in intact cells

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.

Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer.

A new synthetic procedure for the preparation of daunorubicin and adriamycin analogues bearing different substituents on ring D, has been developed. The new compounds display outstanding efficacy against experimental tumours of mice.

Synthesis and antitumour activity of new daunorubicin and adriamycin analogues

Vengono descritte le proprieta di una serie di peptidi sintetici affini all'Eledoisina sia per la struttura che per l'attivita.

Synthetic peptides related to eledoisin

Vengono descritte le proprieta di una serie di peptidi sintetici affini alla ceruleina e si discutono brevemente i rapporti fra attivita e struttura.

Synthetic peptides related to caerulein. 1.

Daunomycin analogues of the formula: ##STR1## wherein when each R 1 is hydrogen, each R is hydrogen, chlorine, bromine, methyl or methoxy and when each R 1 is chlorine, bromine or methyl, each R is hydrogen, are useful in treating various mammalian tumors and are prepared by reacting a daunomycinone derivative of the formula: ##STR2## wherein R and R 1 are as defined above with 1-chloro-2,3,6-trideoxy-3-trifluoroacetamido-4-trifluoroacetoxy-α-L-lyxopyranose in an inert anhydrous organic solvent in the presence of a catalyst and a hydrogen chloride acceptor.

Daunomycin analogues, their preparation and use

Vengono descritte le attivita adrenolitiche di una nuova classe di derivati dell'ergolina di formula generale IV. Uno di questi composti (No. 20) e stato esaminato su diversi reattivi biologici che hanno messo in luce la sua attivita vasodilatatrice e adrenolitica e l'assenza di attivita indesiderate tipiche degli alcaloidi dell'Ergot.

Luigi Bernardi

Papers

Synthesis and antitumour activity of new daunorubicin and adriamycin analogues

Synthetic peptides related to eledoisin

Synthetic peptides related to caerulein. 1.

Daunomycin analogues, their preparation and use

10-Methoxyergoline derivatives as -adrenergic blocking agents.