The muscarinic acetylcholine M1 receptor protein is known to play a role in hippocampal-based and shortterm memory. It has been shown to improve cognition and modify Alzheimer’s disease (AD) properties in animal models. As a result, muscarinic M1 agonism has been identified as a target for AD treatment. Initial drug development programs targeting the muscarinic M1 receptor were curtailed by una...

Muscarinic acetylcholine receptors contain a region encompassing the second and third transmembrane domains that is rich in conserved aspartic acid residues. To investigate the role of four conserved aspartic acids at positions 71, 99, 105, and 122 in muscarinic receptor function, point mutations in the rat m1 muscarinic receptor gene were made that converted each Asp to Asn, and wild type or m...

Incubation of 1321N1 human astrocytoma cells with carbachol resulted in a rapid loss of binding of [3H]N-methylscopolamine ([3H]NMS) to muscarinic cholinergic receptors measured at 4 degrees C on intact cells; loss of muscarinic receptors in lysates from the same cells measured with [3H]quinuclidinyl benzilate [( 3H]QNB) at 37 degrees C occurred at a slower rate. Upon removal of agonist from th...

BACKGROUND Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentatio...

The distributed organization of the human visual cortex calls for a mechanism that integrates and binds the features of a perceived event, and neural synchronization is a prime candidate to serve that purpose. Animal studies suggest that synchronization in the visual cortex is enhanced by the muscarinic cholinergic system. Here we show that in healthy humans the binding of shape and colour, and...

Genomic and cDNA clones encoding a muscarinic acetylcholine receptor from Drosophila melanogaster have been isolated. Sequence analysis demonstrates that this gene encodes a receptor with a high degree of amino acid identity to the mammalian muscarinic acetylcholine receptors and has three introns in the portion of the gene encoding the third putative cytoplasmic loop. A full-length cDNA clone ...

Experiments using muscarinic receptor antagonists were done to determine which muscarinic receptor subtypes(s) mediate carbachol-evoked calcium release in N1E-115 cells. McN-A-343 and a new analog, (+/-)BN228, were weak antagonists and neither compound caused release on its own. The rank order of potency was 4-DAMP greater than pirenzepine greater than AFDX116 greater than (+/-)BN228 and McN-A-...

The i.p. injection of nicotine produced several changes in regional catecholamine concentrations in rat brain. These changes were blocked by the centrally active nicotinic antagonist mecamylamine, but not by the quaternary nicotinic antagonist hexamethonium. An examination of the effects of various cholinergic agents on hypothalamic epinephrine concentrations revealed several interesting findin...

The Morris water maze (MWM) is regarded as one of the most popular tests for detecting spatial memory in rodents. Long-term potentiation and cGMP synthesis seem to be among crucial factors involved this type learning. Muscarinic (M1, M4, M5 receptors) metabotropic glutamate (mGlu) receptors are important targets search antipsychotic drugs with potency treat cognitive disabilities associated dis...

We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly reduced freezing. To test whether cholinergic mani...