Drugs online research references
Pharmacol Biochem Behav. 1999 Feb;62(2):367-80.
Ontogeny of muscarinic cholinergic supersensitivity in the Flinders Sensitive Line rat.
Daws LC, Overstreet DH.
The Flinders University of South Australia, Department of Science and Engineering, School of Biological Sciences, Adelaide, Australia.
The present study examined the ontogeny of muscarinic sensitivity in the Flinders Sensitive Line (FSL) rat, a model for human depression that was selectively bred for increased cholinergic function. In most cases, the FSL rats were more sensitive to the muscarinic agonists, oxotremorine and oxotremorine-M. early postnatally [13 days postpartum (P13)], suggesting that muscarinic supersensitivity is an inherent characteristic of FSL rats. The emergence of increased sensitivity to muscarinic agonists in FSL rats did not correlate with either the emergence of subsensitivity to the muscarinic antagonist, scopolamine, at P60 or with increased muscarinic (M1 or M2) receptor density. Relative to FRL rats, FSL rats did not exhibit increases in muscarinic receptor binding until P32 in the striatum and hippocampus and P120 in the hypothalamus. These results are consistent with the suggestions that (a) muscarinic supersensitivity, which appears early in development, may be associated with depressive disorders, and (b) the differences in muscarinic sensitivity early postnatally cannot be accounted for by an increase in the number of muscarinic receptors, per se.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9972706&dopt=Abstract
musica.mcgill.ca
Detailed information on the outflow pathway of sympathetic vasoconstrictor fibers to the upper extremity is lacking. We studied the organization of the sympathetic innervation of the forelimb resistance vessels and of the sinoatrial (SA) node in the decerebrated, artificially respirated cat. The distal portion of sectioned individual rami T1-8 and the sympathetic chain immediately caudal to T8 on the right side were electrically stimulated while the right forelimb perfusion pressure (forelimb perfused at constant flow) and heart rate were recorded. Increases in perfusion pressure were evoked by stimulation of T2-8 (maximal response T7: 55 +/- 2.3 mm Hg). Responses were still evoked by stimulation of the sympathetic chain immediately caudal to T8 (44 +/- 15 mm Hg). Increases in heart rate were evoked by the stimulation of more rostral rami (T1-5; maximal response T3: 55.2 +/- 8 bpm). These vasoconstrictor and cardioacceleratory responses were blocked by the cholinergic antagonists hexamethonium and scopolamine. Sectioning of the vertebral nerve and the T1 ramus abolished the vasoconstrictor response. Stimulation of the vertebral nerve and of the proximal portion of the sectioned T1 ramus increased perfusion pressure (69 +/- 9 and 34 +/- 14 mm Hg, respectively), which was unaffected by ganglionic cholinergic block. These data suggest that forelimb resistance vessel control is subserved by sympathetic preganglionic neurons located mainly in the middle to caudal thoracic spinal segments. Some of the postganglionic axons subserving vasomotor function course through the T1 ramus, in addition to the vertebral nerve. Implications: Forelimb vasculature is controlled by sympathetic preganglionic neurons located in middle to caudal thoracic spinal segments and by postganglionic axons carried in the T1 ramus and vertebral nerve. This helps to provide the anatomical substrate of interruption of sympathetic outflow to the upper extremity produced by major conduction anesthesia of the stellate ganglion or spinal cord.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9972748&dopt=Abstract
nimr.mrc.ac.uk
The affinity and allosteric properties of 22 quaternary derivatives of strychnine and brucine at the m1-m4 subtypes of muscarinic receptors have been analyzed and compared. The subtype selectivity, in terms of affinity, was in general m2 > m4 > m1 > m3. The highest affinities were found for N-benzyl, N-2-naphthylmethyl, and N-4-biphenylylmethyl strychnine (13, 14, and 18, respectively). All the strychnine and brucine derivatives were positively cooperative with the antagonist, N-methylscopolamine, at m2 receptors and, in the case of the strychnine analogues, were positively cooperative with N-methylscopolamine at least at one other subtype. The strychnine analogues were negatively cooperative with the neurotransmitter, acetylcholine, at all subtypes whereas brucine and five of the six derivatives examined were positively cooperative with acetylcholine at one or more subtypes (m1-m5) and exhibited different patterns of subtype selectivity. The ability to generate subtype-selective allosteric enhancers of acetylcholine binding and function may be of use in the development of drugs for the treatment of Alzheimer's disease.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9986715&dopt=Abstract
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