Drugs, response morphine

Unlike morphine, the action of enkephalins is short-lived. They bind to the cellular receptor and thereby induce the cells to respond. Then they are quickly destroyed by enzymes in the brain that hydrolyze the peptide bonds of the enkephalin. Once destroyed, they are no longer able to elicit a cellular response. Morphine and heroin bind to these same receptors and induce the cells to respond. However, these drugs are not destroyed and therefore persist in the brain for long periods at concentrations high enough to continue to cause biological effects. 

All the drugs tested in these experiments were administered (IP) at doses ranging from 3 to 10 mg/kg (except for ketamine, which was tested at 10, 30, and 100 mg/kg). All the rats used had previously turned contralaterally in response to 0.05 mg/kg apo-morphine HC1. Net ipsilateral rotations were counted in two consecutive 15-minute bins, immediately following drug (or saline) admi ni strati on. ... 

The multiplicity of G proteins coupled to opiate receptors may explain how different opiates can bind to the same receptor yet induce different cellular responses. For example, morphine binds to the cloned rat fi receptor expressed in HEK 293, CHO and COS-7 cells and inhibits cAMP accumulation [80-82]. Morphine can be continuously applied to the cells for up to 16 h, and the potency and magnitude of morphine inhibition of adenylyl cyclase does not diminish [80, 81]. In contrast, the opiate sufentanil can bind to the same cloned fi receptor in HEK 293 cells to inhibit cAMP accumulation. However, sufentanil s actions rapidly desensitize [83]. Since both compounds bind to the same receptor, and the fi receptor is the only receptor these drugs can interact with in these cells, the ability of these two full agonists to differentially regulate the fi receptor must be due to their abilities to affect separate adaptive processes in these cells. 

Before delving into ways the living world uses its special chemicals, we should note that these compounds touch our own lives in important ways. For millennia, humans have been borrowing natural chemicals for their own purposes, most often as drugs. Our oldest medicine is opium, which we prepare from the opium poppy (Papaver somniferum) today much as Mediterranean peoples did four thousand years ago. Just as we do, these early communities valued opium for its ability to kill pain and impart a sense of well-being. The principal constituent responsible for these effects is a chemical compound called morphine, which remains unsurpassed in its ability to control severe pain. In poppies, morphine s toxicity and bitterness presumably repel herbivores looking for a tasty meal. 

Kumar R, Reavill C, Stolerman IP (1987) Nicotine cue in rats effects of central administration of ganglion-blocking drugs, Br J Pharmacol 90 239-246 Lamb RJ, Preston KL, Schindler CW, Meisch RA, Davis F, Katz JL, Henningfield JE, Goldberg SR (1991) The reinforcing and subjective effects of morphine in post-addicts a dose-response study. J Pharmacol Exp Ther 259 1165-1173... 

Pentazocine has been successfully used to relieve labour pain [201] and its obstetric use in place of pethidine is favoured by,its apparent inferior ability to pass the placental barrier [206]. A clinical trial of (+)- and (-)-pentazocine adds to the rare number of examples in which optical enantiomorphs have been evaluated [207]. In post-operative patients, response to 60 mg of the dextro isomer was less than that to 5 mg of morphine, while 25—29 mg of (-)-pentazocine was as effective as 10 mg of morphine. Hence most of the activity of the race-mate resides in the laevo isomer, as anticipated from results in animals [208]. Several studies of the distribution, excretion and metabolism of pentazocine have been made. Peak levels of the tritium-labelled drug (and its c/s-3-chloroallyl analogue) were present in the C.N.S. of a cat within 40 minutes of intramuscular administration [209], the comparable figure for morphine being 2 hours [210]. 

Causes of adverse effects over-dosage (A). The drug is administered in a higher dose than is required for the principal effect this directly or indirectly affects other body functions. For instances, morphine (p. 210), given in the appropriate dose, affords excellent pain relief by influencing nociceptive pathways in the CNS. In excessive doses, it inhibits the respiratory center and makes apnea imminent The dose dependence of both effects can be graphed in the form of dose-response curves (DRC). The distance between both DRCs indicates the difference between the therapeutic and toxic doses. This margin of safety indicates the risk of toxicity when standard doses are exceeded. 

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