Amphetamine antagonizes the presynaptic inhibitory effect of clonidine through an interaction at the level of the alpha 2-adrenoceptors.
1. In the whole rat vas deferens 20 microM noradrenaline (NA) and 0.011 microM clonidine decreased (36 +/- 7.4% and 80 +/- 6.0% respectively) the motor response induced by hypogastric nerve stimulation. These effects were reverted by 1 microM yohimbine. Amphetamine 5.4 microM failed to antagonize the inhibitory effect of NA and attenuated clonidine effect. 2. The effect of amphetamine was not altered by preincubation with either cocaine 1 microM, (-)-propranolol 0.3 microM or cocaine plus prazosin 0.028 microM. 3. In reserpine pretreated animals amphetamine 5.4 microM shifted to the right the concentration-response curve (CRC) to clonidine 0.62 +/- 0.05 log units with a KB value of 1.83 +/- 0.30 microM. 4. Binding of [3H]clonidine and [3H]prazosin were inhibited by amphetamine. Amphetamine was 90 times more potent to inhibit [3H]clonidine binding. 5. The results obtained suggest a possible direct interaction between clonidine and amphetamine on alpha-adrenoceptor.
Fiszman
M L
ML
Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina.
Luchelli-Fortis
M A
MA
Stefano
F J
FJ
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D012110:Reserpine; D000661:Amphetamine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin