[A tribute to Carl Djerassi]. / Tributo a Carl Djerassi.

On January 15, 2015, Carl Djerassi, an extraordinary personality, died at the age of 91 years. He was born in Vienna, Austria, on October 29, 1923. His parents were physicians and probably he wanted to be also a physician, but sooner than later he chose to be a chemist. In 1939 he arrived to live to New York with his mother. In 1945 he became American citizen. Part of his work is the first commercial antihistamine, pyribenzamine, and the first successful combined oral contraceptive pill. With this editorial we make a tribute to this steroid pioneer.

El 30 de enero de 2015 falleció, a la edad de 91 años, Carl Djerassi, un personaje extraordinario. Nació en Viena, Austria, el 29 de octubre de 1923. Sus padres eran médicos y quizás por esa razón él también quería serlo, pero pronto escogió la química. En 1939 llegó con su madre a vivir a Nueva York y en 1945 se naturalizó estadounidense. Son obra suya el primer antihistamínico comercial (la piribenzamina) y el compuesto farmacológico de la píldora anticonceptiva. Sirva el presente editorial como un homenaje a este pionero de los esteroides sintéticos.

Allergic conjunctivitis: the evolution of therapeutic options.

The eye has become the target of intense pharmacologic development because it represents one of the most active sites of allergic inflammation, due to it having no mechanical barrier to prevent the impact of allergens such as pollen on its surface. Over the past 20 years, we have witnessed an astonishing growth in therapeutic advances, ranging essentially from derivatives of simple aspirin to various newly developed biological immunomodulatory agents, using implantable drug delivery devices that exceed the safety and efficacy of those available for other organ systems and resorting to advanced surgical techniques for the correction of sight-threatening, disease-related complications. Overall, with the expanding knowledge base, the intricacy of ocular inflammation appears to be becoming ever more manageable and the clinical allergist/immunologist has an increasing role in the treatment outcomes of patients with anterior inflammatory disorders of the ocular surface primarily allergic conjunctivitis but also including dry eye syndromes.

Histamine and H1-antihistamines: celebrating a century of progress.

In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future.

Next generation antihistamines: therapeutic rationale, accomplishments and advances.

Antihistamines, among the most commonly prescribed drugs in the world, have evolved considerably since the first generation was introduced >50 years ago. The first generation antihistamines (e.g., chlorpheniramine, diphenhydramine, promethazine and hydroxyzine) are still widely available and in use today. These drugs have considerable sedative effects caused by their ability to cross the blood-brain barrier. The next generation of antihistamines to emerge in the market were devoid of these sedative effects; however, two (terfenadine and astemizole) have shown rare but lethal cardiotoxic side effects. The third generation antihistamines, metabolites of the earlier drugs, have demonstrated no cardiac effects of the parent drugs and are at least as potent. Many have exhibited superior pharmacokinetic and pharmacological profiles, including an improved onset of action and duration of effect. The clinical benefit of these newer oral antihistamines will clearly help improve the quality of life of patients with chronic allergies.

Molecular pharmacology of second-generation antihistamines.

Histamine was the first allergic mediator identified in the early part of this century. It has three defined receptors, but most effects of histamine in allergic reactions are through the H1 receptor. The first H1 antagonists were introduced into clinical use in the late 1940s, and drugs of this class are still the preferred initial choice for management of allergic rhinitis and urticaria. The first-generation drugs were characterized by nonspecific binding to many receptors and penetration of the blood-brain barrier, resulting in multiple side effects. Within the central nervous system (CNS), interference with normal histamine binding to the H1 receptor is associated with drowsiness and psychomotor impairment. The second-generation drugs have a much improved benefit/adverse effect profile, largely based on greater potency, receptor specificity, and lower CNS penetration. The potency of antihistamines for blocking H1 receptors can be compared by their inhibition of the cutaneous wheal and flare response to histamine. These drugs seem to have additional antiallergic properties related to blockade of mediator release and interference with cellular recruitment and activation. Clinical trials comparing the efficacy of antihistamines in rhinitis and asthma are reviewed. Recent studies have explored the potential of antihistamines to prevent the progression of allergy and their enhanced efficacy when combined with leukotriene antagonists.

History of modern psychopharmacology: a personal view with an emphasis on antidepressants.

OBJECTIVE: This article provides the chemical basis for the molecular modification of H1 antihistamines in the rational development of some antidepressant and antipsychotic drugs. METHODS: A review of the literature and personal experiences have been compiled. CONCLUSIONS: The contributions of many basic scientists, the crucial observations of clinicians, and the desire of the drug industry to make money have resulted in the currently available psychopharmacological treatments. The future development of psychopharmacology depends on better clinical research to generate new hypotheses of the chemical and behavioral pathology of mental disease. Psychosomatic medicine can make a unique contribution in its interdisciplinary role of stressing brain, body, and mind relationships.

Milestones in the biology and pharmacology of H1-receptor antagonists.

Daniele Bovet's pioneering discovery that a series of compounds possessing anti-histamine activity reduced the symptoms of anaphylaxis provided the proof that histamine plays a pivotal role as a mediator of allergic reactions. Basophils and mast cells are the major sources of histamine in man and they are thus one of the primary effector cells of allergic inflammation. Some H1-receptor antagonists possess a variety of antiinflammatory activity to H1 antagonism in vitro and in vivo. This promising area should be explored further and much remains to be done in the evaluation of the immunomodulatory effects of anti-histamines.

Cetirizina, novo anti-histaminico H1 da segunda geracao / Cetirizin, a new antihistamine H1 of the second generation

Revisao da cetirizina quanto a acao farmacologica,estudo farmacocinetico,uso terapeutico dose e administracao,efeitos adversos,interacao e comparacoa com outros anti-histaminicos da segunda geracao