Drug and Alcohol Rehabilitation: Opioid Peptides: Potential for Drug Development.

Opioid Peptides: Potential for Drug Development.

Filed under: Drug and Alcohol Rehabilitation

Drug Discov Today Technol. 2012; 9(1): e23-e31
Aldrich JV, McLaughlin JP

Opioid receptors are important targets for the treatment of pain and potentially for other disease states (e.g. mood disorders and drug abuse) as well. Significant recent advances have been made in identifying opioid peptide analogs that exhibit promising in vivo activity for treatment of these maladies. This review focuses on the development and evaluation of opioid peptide analogs demonstrating activity after systemic administration, and recent clinical evaluations of opioid peptides for possible therapeutic use.
HubMed – drug

 

A novel synthesis of 1-aryl-3-piperidone derivatives.

Filed under: Drug and Alcohol Rehabilitation

Tetrahedron Lett. 2013 Feb 6; 54(6): 573-575
Zhang Y, Silverman RB

A novel method to construct the 1-aryl-3-piperidone scaffold is described here. Starting from 3,5-dichloroaniline, a seven-step synthesis, without the use of protecting groups, generates the desired 3-piperidone ring in an overall yield of 30% through a key Morita-Baylis-Hillman reaction and ring-closing metathesis, providing easy access to diverse and useful heterocycles.
HubMed – drug

 

Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo.

Filed under: Drug and Alcohol Rehabilitation

Am J Physiol Heart Circ Physiol. 2013 Jan 11;
Kockova R, Svatunkova J, Novotny J, Hejnova L, Ostadal B, Sedmera D

A significant increase in cardiovascular medication use during pregnancy occurred in recent years. Only limited evidence on safety profiles is available and little is known about the mechanisms of adverse effect on the fetus. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. Embryotoxicity was tested in ovo after administration of various doses of metoprolol, carvedilol, or ivabradine. Embryonic day (ED) 4 and 8 chick embryos were studied by video microscopy and ultrasound biomicroscopy ex ovo after intraamniotic injection of the drug for a period of 30 minutes. Stroke volume was calculated by the Simpson method and prolate ellipsoid formula. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of ?-adrenergic receptors showed a downward tendency during embryonic development. A negative chronotropic effect of metoprolol, carvedilol and ivabradine was increasingly pronounced with embryonic maturity despite a downward trend in the number of ?-adrenergic receptors. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death. While standard doses of these drugs appear relatively safe, high doses have a potentially adverse effect on the fetus through reduced heart rate.
HubMed – drug

 

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