Details of Drug Interaction | MecDDI

Drug General Information (ID: DDITBL5NVA)
Drug Name			Pimozide		Drug Info		Metamfetamine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antipsychotic Agents				Cns Stimulants
Structure

Mechanism of Pimozide-Metamfetamine Interaction (Severity Level: Major)
Antagonize the effect of dopaminergic agents Click to Show/Hide Mechanism Graph

Drug Name		Pimozide				Metamfetamine
Mechanism		Antidopaminergic effects Dopamine receptor Antagonist				Dopaminergic effects Dopamine transporter Inhibitor
Key Mechanism Factor 1
		Factor Name		Dopamine receptor				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Dopamine transporter				× Structure Sequence MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDRETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELALGQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQLTACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSVDFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSSGFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGIDSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAAGTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSIVTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKDRELVDRGEVRQFTLRHWLKV
		Gene Name		SLC6A3
		Uniprot ID		SC6A3_HUMAN
		KEGG Pathway		hsa:6531
		Protein Family		Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
		Protein Function		Amine transporter (PubMed:1406597, PubMed:8302271, PubMed:15505207). Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity). Click to Show/Hide
Mechanism Description		Antagonize the effect of Metamfetamine when combined with Pimozide

Recommended Action
Management		When treating Tourette's disorder, the use of pimozide in patients receiving drugs that may cause motor and phonic tics (e.g., amphetamines, methylphenidate, pemoline) is considered contraindicated until such patients have been withdrawn from these drugs to determine whether they are, in fact, responsible for the tics.

References
1	Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57. [PMID: 10668858]
2	Product Information. Orap Tablets (pimozide). Gate Pharmaceuticals, Sellersville, PA.