Alzheimers disease and cognition

Extensive literature suggests that the brain histaminergic system can modulate learning and reinforcement. However, many details are lacking, and some findings seem contradictory. For example, several workers have found that microinjections of HA into certain brain areas facilitate cognitive performance and task recall, and pharmacological depletion of brain HA has the opposite effect (Kamei et al. 1993 Leurs et al. 1998). Furthermore, both H1 receptor agonists, and an inhibitor of brain HA...

Interactions between G proteins and GPCRs

G proteins bind to their corresponding GPCRs at multiple sites on the cytoplasmic regions of the receptor. Several regions of Ga contribute toward association with GPCRs, which have been extensively reviewed (Gudermann etal. 1997 Bourne 1997 Hamm 1998). One of the major domains for receptor recognition is the C-terminus of Ga, where PTX-mediated ADP-ribosylation of Gi subfamily members occurs and the receptor-G protein interaction is then disrupted. Replacement of the last five amino acids of...

Anxiety

The initial suggestion that the CCK system might be involved in anxiety came from experiments of Bradwejn and de Montigny (1984) showing that benzodiazepine receptor agonists could attenuate CCK induced excitation of rat hippocampal neurones. Subsequent clinical studies demonstrated that bolus injections of the CCK2 receptor agonist CCK4 or pentagastrin provoke panic attacks in patients with panic disorders (Bradwejn et al. 1991, 1992). Recent investigations have revealed that the panicogenic...

References

Andres ME, Burger C, Peral-Rubio MJ, Battaglioli E, Anderson ME, Grimes J etal. (1999). CoREST A functional corepressor required for regulation of neural-specific gene expression. Proc Natl Acad Sci USA 96, 9873-8. Archer TK, Lefebvre P, Wolford RG, and Hager GL (1992). Transcription factor loading on the MMTV promoter a bimodal mechanism for promoter activation published erratum appears in Science 1992 Apr 10 256(5054) 161 . Science 255, 1573-6. ArranzB, Rosel P, Ramirez N, and San L (2001)....

Peripheral indications

HA can produce a wide variety of powerful physiological changes as a result of activation of H1 receptors. Diseases involving mast cells such as urticaria pigmentosa or systemic mas-tocytosis also show many of these responses. Patients with allergies also experience many of these symptoms. It has been known for many years that HA is potent spasmogen on intestinal and bronchiolar smooth muscle, actions which are mediated predominantly by H1 receptors Ash and Schild 1966 . Asthmatics show...

Epilepsy

The discovery of galanin's effects on epilepsy, where it acts as an anticonvulsant, is a good example of the pre-synaptic inhibitory effects of galanin on glutamate but not on GABA release Ben-Ari 1990 , and shows how it acts as a postsynaptic hyperpolarizing substance to reduce run-away discharges alike Mazarati et al. 1992, 1998, 2000, 2001 . The galanin agonist, galnon, suppresses phenyltetrazole-induced 40 mg kg seizures when injected i.p. 2 mg kg Saar, 2002 . Additional information on the...

Synthesis Of Zolantidine

Synthesis Zolantidine

Drugs which act at the H1 receptor have been known for many years. Discovery of the first HA antagonist over fifty years ago led to an increased understanding of anaphylaxis and allergy, set the stage for demonstrating the likely existence of more than one type of HA receptor, and indirectly led to the subsequent development of phenothiazines and tricyclic antidepressants Green 1983 . Hundreds of the so-called 'classical' or first-generation H1-antagonists have been developed and many are still...